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"Polimorfisme CYP2C19 menurunkan metabolisme klopidogrel dan telah diketahui meningkatkan mortalitas serta kejadian kardiovaskular mayor. VerifyNow P2Y12 merupakan salah satu pemeriksaan yang secara spesifik menggambarkan fungsi platelet terhadap agen penghambat P2Y12 yang dikonsumsi. Hubungan antara polimorfisme CYP2C19 dengan TIMI flow pada populasi Asia, khususnya Indonesia, belum pernah dilakukan.Penelitian ini bertujuan untuk mengetahui hubungan antara polimorfisme CYP2C19 terhadap fungsi penghambatan platelet dan TIMI flow, serta hubungan antara fungsi penghambatan platelet dan TIMI flow.Dilakukan pemeriksaan polimorfisme CYP2C19 dengan menggunakan metode Taqman dan pemeriksaan fungsi penghambatan platelet yang diukur dengan VerifyNow P2Y12 pada 90 pasien IMA-EST yang menjalani IKPP yang memenuhi kriteria penelitian.Dari 90 subyek penelitian, studi polimorfisme genetik mengungkapkan 23,3% pasien dengan alel * 2, 11,2% dari * 3 alel pembawa, dan 1,1% membawa kedua alel. 24,4% pasien tergolong non-responder terhadap klopidogrel. Secara keseluruhan tidak terdapat hubungan secara langsung antara polimorfisme CYP2C19 dengan TIMI flow 3, namun terdapat hubungan antara polimorfisme CYP2C19 dengan penurunan fungsi penghambatan platelet (OR 4.7, p = 0.030). Indeks reaktivitas platelet >208 PRU meningkatkan risiko TIMI flow < 3 (OR 3.3, p= 0.046).Tidak terdapat hubungan secara langsung antara polimorfisme CYP2C19 dengan TIMI flow, namun pasien dengan polimorfisme CYP2C19*2 dan/atau *3 memiliki risiko untuk mengalami penurunan penghambatan fungsi platelet. Pasien yang tergolong non-responder terhadap klopidogrel ini juga berisiko untuk mendapatkan reperfusi miokard yang suboptimal.

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CYP2C19 polymorphism plays an important role in clopidogrel metabolism. The genetic factor is VerifyNow P2Y12 is an examination that specifically describes platelet function against P2Y12 inhibitors. It is unknown whether platelet reactivity measured by P2Y12 reaction unit (PRU) is affected by CYP2C19 polymorphism or predictive of TIMI flow in Asian populations, particularly in Indonesia. We sought to define whether polymorphisms on CYP2C19 genes and platelet reactivity may affect the myocardial perfusion.

STEMI patients who underwent primary PCI and has received 600 mg loading dose of clopidogrel were recruited for the study. We measured platelet reactivity by VerifyNow P2Y12, high platelet reactivity was defined as > 208 PRU. Genetic polymorphisms analysis to assess the presence of CYP2C19*2 and *3 alleles on each patient were performed by Taqman method.

There were 90 patients recruited for study. Genetic polymorphisms studies revealed 23.3% of patients with *2 allele, 11.2% of *3 allele carriers, and 1.1% carried both allele. 23.4% of patients were clopidogrel non-responders. Overall, there was no correlation between CYP2C19 polymorphism and TIMI flow < 3, but there was a relationship between CYP2C19 polymorphism and decreased function of platelet inhibition (OR 4.7, p = 0.030). Platelet reactivity index > 208 increased the risk of suboptimal reperfusion (OR 3.3, p = 0.046).

There is no direct relationship between CYP2C19 polymorphism and TIMI flow, but patients with CYP2C19*2 and/or CYP2C19*3 had increased risk of being clopidogrel non responders. After adjusted to confounding factors, VerifyNow > 208 PRU is associated with suboptimal myocardial reperfusion."

"STEMI adalah IMA dengan risiko mortalitas tinggi. Risiko dikurangi dengan revaskularisasi berupa IKPP Gangguan kardiovaskular dikaitkan dengan penurunan konsentrasi vitamin D. Penurunan bisa disebabkan SNP gen CYP27B1 yang mengkode enzim 1α hidroksilase dan belum ada penelitian yang menghubungkan konsentrasi vitamin D pada pasien STEMI yang menjalani IKPP. Hasil IKPP berupa area sumbatan dan kemampuan darah mengalir ke pembuluh darah koroner, dikenal dengan TIMI grade 0-3. Penelitian bertujuan untuk menganalisis hubungan konsentrasi kalsidiol dan gen CYP27B1 (-rs10877012) perubahan G ke T pada pasien STEMI yang menjalani IKPP dengan aliran TIMI akhir. Seratus subjek STEMI dan kontrol diambil 3 mL darah. Plasmanya diukur konsentrasi kalsidiol dengan teknik ELISA. PBMC dianalisis gen CYP27B1 (- rs10877012) dengan qRT PCR teknik Taqman Probe. Data dianalisis statistik kemaknaan 0,05. Konsentrasi kalsidiol median kasus 35,94 ng/ml dan kontrol 20,89 ng/ml berbeda bermakna (p=0,0001). Variasi gen CYP27B1 pada kedua kelompok berbeda bermakna (p=0,0001), dengan polimorfisme TT kasus 28% dan kontrol 19%. Hubungan konsentrasi kalsidiol dengan polimorfisme gen CYP27B1 berbeda bermakna (p=0,0001), tidak terdapat hubungan konsentrasi kalsidiol dengan aliran TIMI dan polimorfisme gen CYP27B1 dengan p=0,232. Konsentrasi kalsidiol tinggi pada kasus dimungkinkan sebagai respon tubuh terhadap inflamasi yang mengalami serangan jantung. Polimorfisme TT kasus 28% tidak memiliki hubungan terhadap patofisiologi aliran TIMI akhir.

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STEMI is an AMI with a high risk of mortality. The risk is reduced by revascularization called by IKPP Cardiovascular disorders are associated with decreased vitamin D concentrations. The decrease could be due to the SNP gene CYP27B1 which encodes the enzyme 1α hydroxylase and no studies have linked vitamin D concentrations in STEMI patients undergoing IKPP. IKPP results in the form of block area and the ability of blood to flow to the coronary blood vessels, known as TIMI grade 0-3. The aim of this study was to analyze the relationship between calcidiol concentrations and the CYP27B1 gene (-rs10877012) G to T changes in STEMI undergoing IKPP with TIMI flow. One hundred STEMI and control subjects collected 3 mL of blood. Plasma concentration of calcidiol was measured using the ELISA technique. PBMCs were analyzed CYP27B1 gene (- rs10877012) by taqman probe qRT PCR. Data were analyzed by statistical significance of 0.05. Median calcidiol concentration of 35.94 ng / ml cases and 20.89 ng / ml controls was significantly different (p = 0.0001). CYP27B1 gene variation in the two groups was significantly different (p = 0.0001), with TT polymorphism of 28% and 19% of controls. The correlation between calcidiol concentration and CYP27B1 gene polymorphism was significantly different (p = 0.0001), there was no correlation between calcidiol concentration and TIMI flow and CYP27B1 gene polymorphism with p = 0.232. The high calcidiol concentration in this case may be the body's response to inflammation following a heart attack. The TT polymorphism of 28% cases had no relationship to the pathophysiology of late TIMI flow."

"Latar belakang: Polimorfisme genetik dari reseptor P2Y12 dikatakan dapatmempengaruhi aktivasi reseptor P2Y12 atau menghambat aktivasi trombosit. Beberapapolimorfisme nukleotida tunggal dalam gen P2Y12 ditemukan dapat menyebabkanvariabilitas antarindividu dalam agregasi platelet. Telah diidentifikasi limapolimorfisme dari gen P2Y12 yaitu T744C, C34T, G52T, ins801A, dan C139T. Salahsatunya, polimorfisme C34T adalah salah satu dari polimorfisme yang dikatakan adakaitannya dengan peningkatan agregasi platelet yang dapat menunjukkan kemungkinanuntuk terjadinya modifikasi respon terapi clopidogrel. Namun hingga saat ini belumada penelitian yang menilai hubungan langsung antara polimorfisme reseptor P2Y12dengan TIMI-flow beserta faktor-faktor yang mempengaruhinya, termasuk fungsipenghambatan platelet pada pasien IMA-EST yang menjalani IKPP.Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan antara polimorfismenukleotida tunggal pada reseptor P2Y12 dengan TIMI flow beserta faktor-faktor yangmempengaruhinya, termasuk penghambatan fungsi platelet.Metode: Studi potong lintang pada 167 pasien IMA-EST yang menjalani IKPP.dilakukan pemeriksaan polimorfisme C34T reseptor P2Y12 dengan metode Taqmandan pemeriksaan fungsi penghambatan platelet yang diukur dengan VerifyNow P2Y12.Hasil: Dari 167 subjek penelitian, studi polimorfisme mengungkapkan proporsi pasiendengan heterozygous mutan sebanyak 34.1%, dan 1.8% pasien merupakan homozygousmutan. Sisanya adalah homozygous wildtype ditemukan sebanyak 64.1%. 25.7% pasientergolong non-responder terhadap clopidogrel. Secara keseluruhan tidak terdapathubungan secara langsung antara polimorfisme C34T dengan TIMI flow < 3, namunterdapat hubungan antara polimorfisme C34T dengan penurunan fungsi penghambatanplatelet (OR 2.17, p = 0.046).Kesimpulan: Tidak terdapat hubungan secara langsung antara polimorfisme C34Tdengan TIMI flow, namun pasien dengan polimorfisme C34T pada reseptor P2Y12memiliki risiko untuk mengalami penurunan penghambatan fungsi platelet.

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Background: Genetic polymorphism of P2Y12 receptors is said to have affect of

P2Y12 receptor activation or inhibit platelet activation. Several single nucleotide

polymorphisms in the P2Y12 gene were found to cause variability between individuals

in platelet aggregation. Five polymorphisms have been identified from the P2Y12 gene,

namely T744C, C34T, G52T, ins801A, and C139T. One of them, C34T is one of the

polymorphisms that is said to be related to increased platelet aggregation which can

indicate the possibility for modification of the response of clopidogrel therapy. But until

now there has been no research that assesses the direct relationship between P2Y12

receptor polymorphisms and TIMI-flow along with the factors that influence it,

including the function of platelet inhibition in STEMI patients undergoing PPCI

Objective: This study aims to determine the relationship between single nucleotide

polymorphisms at P2Y12 receptors with TIMI flow along with the faktors that

influenced it, including inhibition of platelet function.

Methods: A cross-sectional study of 167 STEMI patients who underwent PPCI. C34T

polymorphism of P2Y12 receptor was evaluated by the Taqman method and the

inhibition of platelet function was measured by VerifyNow P2Y12.

Results: Among 167 subjects, the heterozygous mutants group were 34.1%, and 1.8%

of patients were homozygous mutants. The rest 64.1% was homozygous wildtype.

25.7% of patients were classified as non-responders to clopidogrel. Overall there was

no direct relationship between C34T polymorphisms and TIMI flow <3, but there was

a relationship between C34T polymorphisms and decreased platelet inhibitory function

(OR 2.17, p = 0.046).

Conclusion: There is no direct relationship between C34T polymorphisms and TIMI

flow, but patients with C34T polymorphisms of P2Y12 receptors have a risk of

decreasing platelet function inhibition."

"Latar belakang: Resistensi klopidogrel merupakan salah satu faktor risiko penting terjadinya kejadian iskemik berulang pada pasien yang telah mendapat terapi anti platelet yang optimal. Penelitian ini bertujuan untuk mengetahui peran metilasi DNA gen CYP2C19 sebagai salah satu faktor epigenetik terhadap kejadian resistensi klopidogrel pada pasien infark miokard akut dengan elevasi segmen ST (IMA-EST) yang menjalani intervensi koroner perkutan primer (IKPP).Metode: Pasien IMA-EST yang menjalani IKPP diberikan antiplatelet klopidogrel dan menjalani pemeriksaan fungsi platelet degan VerifyNowTM. Kriteria untuk mendefinisikan resistensi klopidogrel adalah nilai PRU >208. Pemeriksaan metilasi DNA gen CYP2C19 dilakukan dengan metode bisulfite genomic sequencing technology. Data klinis, laboratorium, dan angiografik termasuk TIMI flow dikumpulkan untuk dilakukan analisis.Hasil: Dari 122 subjek, resistensi klopidogrel ditemukan pada 22% subjek. Kelompok dengan presentase metilasi DNA <50% mempunyai risiko lebih tinggi terjadinya resistensi klopidogrel (OR 4.5 IK95% 2.1-9.3, nilai p 0.018). Grup ini juga diketahui mempunyai TIMI flow post-IKPP yang suboptimal (OR 3.4 IK95% 1.3 - 8.7, nilai p 0.045).Kesimpulan: Hipometilasi DNA gen CYP2C19 meningkatkan risiko terjadinya resistensi klopidogrel dan luaran klinis yang lebih buruk.

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Background: Clopidogrel resistance is an important risk factor of recurrence of ischemic event after optimal antiplatelet therapy. We aimed to investigate the role of DNA methylation of CYP2C19 gene as one of epigenetic factor to the risk of clopidogrel resistance in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI).

Methods: STEMI patients undergoing PPCI were pretreated with clopidogrel, and their platelet function was measured using VerifyNowTM assay. The criteria for high on- treatment platelet reactivity (HPR) was defined according to the expert consensus criteria (PRU >208). DNA methylation of the CYP2C19 gene was performed using bisulfite genomic sequencing technology. Furthermore, clinical, laboratory and angiographic data including TIMI flow were collected.

Result: Among 122 patients, clopidogrel resistance was found in 22% patients. After dividing into two groups, methylation <50% was associated with increased risk of clopidogrel resistance (OR 4.5 95%CI 2.1-9.3, P value 0.018). This group also found to have suboptimal post-PCI TIMI flow (OR 3.4 95%CI 1.3 - 8.7, P value 0.045).

Conclusions: The lower DNA methylation level of the CYP2C19 gene increases the risk of clopidogrel resistance and subsequent poorer clinical outcome."

"Latar belakang: micro-RNA saat ini telah diketahui berperan dalam patofisiologi berbagai penyakit termasuk di bidang kardiovaskular. miR-26a platelet dikaitkan dengan aktifitas platelet tinggi.Resistensi klopidogrel telah diketahui memiliki prevalensi yang cukup tinggi di populasi Asia, yang mana dapat mempengaruhi mortalitas serta kejadian kardiovaskular mayor. Hubungan antara ekspresi miR-26a platelet dengan resistensi klopidogrel begitu pula dengan TIMI flow pasca IKPP pada IMA-EST di populasi Asia, belum pernah dilaporkan. Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan antara ekspresi miR-26a platelet terhadap reaktivitas platelet dan perfusi miokardium pasca IKPP. Metode: Pada pasien IMA-EST yang menjalani IKPP dan mendapatkan terapi dosis loadingklopidogrel 600 mg, dimasukkan kedalam populasi penelitian. Kami mengukur reaktivitas platelet dengan menggunakan VerifyNow P2Y12, aktifitas platelet tinggi didefiniskan jika memiliki nilai > 208 PRU. Metode RealtimePCR Taqman dilakukan untuk analisa ekspresi miR-26a platelet. Ekspresi miR-26a platelet dan reaktivitas platelet dikorelasikan dengan TIMI flowpasca IKPP pada pasien IMA-EST. Hasil: Terdapat 100 subyek yang direkrut pada studi ini. Diantaranya, 59% menunjukkan peningkatan ekspresi miR-26a. Reaktifitas platelet meningkat pada 27 % pasien studi ini dikategorikan non-responder terhadap klopidogrel. Terdapat hubungan antara ekspresi dengan penurunan fungsi penghambatan platelet (OR 4.2, p = 0.006). Indeks reaktivitas platelet >208 PRU meningkatkan risiko TIMI flow < 3 (OR 3.3, p= 0.015). Tidak terdapat hubungan langsung antara ekspresi miR-26a platelet dan TIMI flow < 3. Kesimpulan: Pasien dengan peningkatan ekspresi miR-26a platelet memiliki risiko untuk mengalami menjadi non-responderklopidogrel. Tidak terdapat hubungan langsung antara ekspresi miR-26a platelet dan TIM flowpasca IKPP.

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Background: micro-RNA has now been known to play a role in the pathophysiology of various diseases including cardiovascular disease. Clopidogrel resistance has been known prevalent in Asian population, that may affect mortality and major cardiovascular events. The relationship between the expression of platelet miR-26a and clopidogrel resistance as well as TIMI flow post primary PCI in STEMI among Asian populations, has never been done.

Objective: the aim of this study is to define whether miR-26a platelet expression has a relation with platelet reactivity and myocardial perfusion after primary PCI.

Methods: STEMI patients who underwent primary PCI and has received 600 mg loading dose of clopidogrel were recruited for the study. We measured platelet reactivity by VerifyNow P2Y12, high platelet reactivity was defined as > 208 PRU. Realtime PCR by taqman method were performed to asses the expression of miR-26a platelet. miRNA-26a platelet expression and platelet reactivity were correlated with TIMI flow post primary PCI in STEMI.

Hasil: there were 100 patients recruited for this study. among them, 59% of patients with high expression of miR-26a platelet. Platelet reactivity showed 27% of the patients were clopidogrel non-responders. There was a relationship between high miR-26a expression and decreased function of platelet inhibition (OR 4.2, p = 0.006). Platelet reactivity index > 208 increased the risk of suboptimal reperfusion (OR 3.3, p = 0.015). There was no direct correlation between miR-26a expression and TIMI flow < 3.

Conclusion: Patients with high miR-26a platelet expression had increased risk of being clopidogrel non responders. There is no direct relationship between miR-26a platelet expression and TIMI flow after primary PCI."

"Studi mengenai pemberian klopidogrel sebelum angiografi koroner (pretreatment) pada pasien infark miokard akut dengan elevasi segmen ST (IMA-EST) yang akan menjalani intervensi koroner perkutan primer (IKPP) terbatas, namun dapat disimpulkan bahwa aman dan dapat penurunan angka major adverse cardiovascular events (MACE). Pada studi yang dilakukan beberapa tahun terakhir, manfaat pemberian klopidogrel pretreatment dipertanyakan. Studi yang telah ada dilakukan di negara lain berbeda dengan kondisi di Indonesia; terdapat perbedaan karakteristik seperti waktu onset nyeri dada hingga pasien sampai ke fasilitas kesehatan primer, loading antiplatelet, serta dilakukan tindakan IKPP yang lebih panjang. Penelitian ini bertujuan untuk mengetahui hubungan pemberian klopidogrel pretreatment  dengan TIMI-flow pasien IMA EST yang menjalani IKPP. Studi potong lintang retrospektif terhadap 220 pasien IMA EST dilakukan di rumah sakit Jantung dan Pembuluh Darah Harapan Kita sejak tanggal 1 Januari - 30 Oktober 2018 dengan membagi subjek dalam kelompok klopidogrel pretreatment (600 mg klopidogrel diberikan > 120 menit sebelum angiografi koroner) dan kelompok yang diberikan < 120 menit. Analisis multivariat menunjukkan bahwa klopidogrel pretreatment merupakan prediktor utama yang mempengaruhi TIMI flow sebelum tindakan IKPP (OR 0.273, 95% CI 0.104-0.716; p=0.008). Pemberian klopidogrel pretreatment berhubungan dengan TIMI flow sebelum tindakan IKPP, namun tidak berpengaruh terhadap TIMI setelah dilakukan tindakan IKPP. 

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Immediate antiplatelet administration is the standard therapy used in acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Studi on clopidogrel pretreatment are limited, but it can be concluded that was safe, also reduced the number of major adverse cardiovascular events (MACE). Recently, pretreatment with P2Y12 are questioned. There are differences in the background and the conditions between the studies that have been conducted and the condition in Indonesia; such as duration of angina onset until arrive at primary health care, time of loading antiplatelet and longer ischemic time.

This study sought to evaluate the association between clopidogrel pretreatment and TIMI flow of patients with acute STEMI undergoing primary PCI. Single-center retrospective cross sectional study of 220 patients with acute STEMI were conducted in National Centre of Cardiovascular Harapan Kita, Indonesia from 1 January-30 October 2018. Subjects are devided into two groups: clopidogrel pretreatment (≥ 120 minute from coronary angiography conducted) and non pretreatment group (<120 minute). Multivariate analysis revealed that clopidogrel pretreatment is the main predictor of preprocedural TIMI grade flow (OR 0.273, 95% CI 0.104-0.716; p=0.008). Clopidogrel pretreatement was associated with TIMI flow grade pre intervention, but not with TIMI flow grade post intervention."

"ABSTRAKLatar belakang: Salah satu faktor yang dicurigai berperan dalam mekanisme resisensi klopidogrel adalah faktor epigenetik seperti metilasi DNA. Individu dengan resistensi klopidogrel ini memiliki kecenderungan untuk mengalami luaran kardiovaskular yang lebih buruk. Nilai TIMI flow pasca IKPP telah diketahui berkaitan dengan luaran klinis pada pasien IMA-EST. Sampai saat ini belum ada penelitian yang menghubungan antara metilasi gen P2Y12 dengan penghambatan fungsi platelet dan nilai TIMI flow pasca IKPP pada pasien IMA EST. Tujuan: Untuk mengetahui hubungan antara metilasi gen reseptor P2Y12 terhadap fungsi penghambatan platelet dan nilai TIMI flow pasca IKPP pada pasien IMA EST. Metode: Sebanyak 118 pasien IMA-EST yang menjalani IKPP dan mendapatkan terapi klopidogrel dimasukkan kedalam populasi penelitian. Dilakukan pemeriksaan VerifyNow P2Y12 dan pemeriksaan metilasi P2Y12. Selanjutnya dilakukan analisis hubungan antara metilasi P2Y12 dengan nilai Verifynow P2Y12 dan TIMI flow pasca IKPP. Hasil: Dari seluruh subyek, 22% diantaranya termasuk klopidogrel nonresponder dan 30% memiliki nilai TIMI flow kurang dari 3. Terdapat 48% subyek yang tidak mengalami metilasi dan 19% subyek mengalami metilasi sempurna pada gen P2Y12. Tidak terdapat hubungan bermakna antara metilasi P2Y12 dengan nilai Verifynow P2Y12 dan TIMI flow pasca IKPP. Nilai Verifynow P2Y12 yang tinggi berhubungan dengan TIMI flow kurang dari 3 pasca IKPP (p=0,043). Kesimpulan: Tidak terdapat hubungan bermakna antara pola metilasi gen P2Y12 dengan penghambatan fungsi platelet dan nilai TIMI flow pasca IKPP. Pasien yangnon-responder terhadap klopidogrel berisiko untuk mendapatkan reperfusi miokard yang suboptimal.

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ABSTRACTBackground: Mechanism of clopidogrel resistance is not well understood yet. In the other hand, epigenetic modifications such as DNA methylation, are suspected to play role in clopidogrel resistence. Subject with high on treatment clopidogrel reactivity show worsen cardiovascular outcome. Meanwhile, TIMI flow after reperfusion are known to be related with poor outcome. Study that evaluate the relationship between methylation of P2Y12 gene with Platelet Reactivity and TIMI-flow after Primary Percutaneous Coronary Intervention (PPCI) in Patients With Acute ST-segment Elevation Myocardial Infarction in South East Asia Population has never been done. Objectives: to define whether methylation of P2Y12 gene and platelet reactivity may affect the myocardial perfusion after PPCI. Methods: There were 118 of STEMI patients who underwent PPCI and had received clopidogrel were recruited for the study. We measured platelet reactivity using Verifynow P2Y12 and Methylation of P2Y12 gene. The relationship among variables are assessed using statistic method. Results: Among 118 subject, 22% are clopidogrel nonresponder and 30% had TIMI flow less than 3. Median of Methylation degree was 15% with 48% subject were unmethylated, 19% subject had 100% methylation. There are no relationship between methylation of P2Y12 gene with platelet reactivity and TIMI flow after PPCI among subjects. The value of Verifynow P2Y12 more than 208 were related TIMI flow less than 3 after PPCI (p=0,043). Conclusion: There are no relationship between methylation of P2Y12 gene with platelet reactivity and TIMI flow after PPCI among subjects. Clopidogel nonresponder subjects were more likely to have suboptimal reperfusion after PPCI"

"Latar Belakang: Orofacial cleft merupakan salah satu dari banyak malformasi bawaan lahir yang sering terjadi pada manusia. Keadaan ini ditandai dengan kelainan morfologi yang dapat mengubah struktur wajah dan mempengaruhi struktur anatomi, juga fungsi otot dengan tingkat keparahan yang bervariasi. Adapun, penyebab celah bibir dan palatum ini dihasilkan dari banyak faktor, dimana terjadi kombinasi antara faktor genetik dan faktor lingkungan.Tujuan: Mengetahui distribusi polimorfisme gen Wnt10a C392T pada penderita orofacial cleft.Metode: Analisis polimorfisme gen Wnt10a C392T dilakukan dengan metode PCR-RFLP dengan enzim restriksi AfeI.Hasil: Menggunakan 25 sampel orofacial cleft dan 75 sampel kontrol, ditemukan 25 sampel orofacial cleft memiliki genotip TT 100 , 20 sampel kontrol memiliki genotip CC 26,6 , 53 sampel memiliki genotip CT 70,6 , dan 2 sampel memiliki genotip TT 2,8 . Tidak ditemukan alel C pada sampel orofacial cleft, semenatara sampel kontrol memiliki 91 alel C 60,7 dan 59 alel T 39,3.Kesimpulan: Terdapat perbedaan bermakna pada distribusi genotip dan alel polimorfisme Gen Wnt10a C392T antara penderita orofacial cleft dan kontrol p value genotip = 0,003, p value alel =0,001.

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Background: Orofacial cleft is one of the many congenital malformations that often occur in humans. It is characterized by morphological abnormalities that can alter the facial structure and affect the anatomical structure, as well as muscle function with variations of severity. The cause of orofacial cleft is generated from many factors, where there is a combination of genetic factors and environmental factors.

Aim: To describe the distibution of Wnt10a C392T gene polymorphism in orofacial cleft patients.

Methods: Analysis of Wnt10a C392T gene polymorphism was performed by PCR RFLP method with AfeI restriction enzyme.

Results: Using 25 orofacial cleft samples and 75 control samples, 25 orofacial cleft samples had 25 TT genotype 100 , 20 control samples had CC genotype 26,6 , 53 samples had CT genotype 70,6 , and 2 samples had TT genotype 2,8 . No C alleles were found in orofacial cleft samples, while control samples had 91 C allele 60,7 and 59 T alleles 39,3.

Conclusions: There were significant differences in genotype distribution and allele of Wnt10a C392T gene polymorphism between orofacial cleft and control patients p value genotype 0.003, p value allele 0.001."

"Infertilitas adalah keadaan dimana selama 12 bulan atau lebih hubungan seks tanpa proteksi tidak dapat menghasilkan keturunan. Di Indonesia sendiri masalah ini didasari oleh faktor dari pihak lelaki sebanyak 25%. Infertilitas pada pria dapat disebabkan oleh faktor internal dan eksternal. Faktor internal antara lain adalah faktor genetik. Salah satu dari faktor genetik adalah mutasi pada gen yang mengkode enzim Methylenetetrahydrofolate Reductase (MTHFR), yang merupakan enzim yang berperan penting dalam proses spermatogenesis. Mutasi ini terdapat pada posisi 677 yaitu perubahan alel C menjadi T yang disebut juga polimorfisme. Penelitian cross-sectional ini bertujuan untuk membuktikan apakah ada hubungan antara polimorfisme gen MTHFR SNP C677T dengan Oligozoospermia. Teknik yang digunakan pada penelitian ini adalah PCR-RFLP untuk isolasi dan amplifikasi DNA. Proses cutting DNA menggunakan enzim HinfI. Selanjutnya data dianalisis menggunakan perhitungan chi-square. Didapat hasil cutting 3 genotip (CC, CT, TT) yang menunjukkan bahwa ada hubungan bermakna antara distribusi ketiga genotip gen MTHFR C677T dan Oligozoospermia dengan p value 0.011 (p<0.05). Hasil serupa ditemukan juga pada distribusi alotip (alel C dan T) yang menunjukkan bahwa ada hubungan bermakna antara distribusi alotip dan Oligozoospermia dengan p value 0.005 (p<0.05). Dapat disimpulkan bahwa polimorfisme gen MTHFR pada posisi C677T berhubungan dengan terjadinya oligozoospermia pada pria Indonesia.

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Infertility is a condition in which 12 months or more unprotected sex fail to produce offspring. In Indonesia this condition is dominated by male infertility with the rate of 25% of all infertility cases. Male infertility can be due to internal and external factors. Internal factors include genetic factors. One of the genetic factors is mutation in gene that codes for Methylenetetrahydrofolate Reductase (MTHFR) enzyme, which is an enzyme that plays an important role in spermatogenesis process. This mutation is located in position 677, which changed allele C into T, called polymorphism.

This cross - sectional study aims to prove whether there is any association between MTHFR gene polymorphism C677T SNP and Oligozoospermia. PCR - RFLP was used for the isolation and amplification of DNA. The DNA cutting process uses Hinf1 enzyme. Furthermore, the data were analyzed with the chi - square calculations.

As a result 3 genotype cutting were obtained (CC, CT, TT) which indicates that there is a significant association between the distribution of the three genotypes of MTHFR C677T and Oligozoospermia genes with p value of 0.011 (p<0.05). Similar results were also found on the allotype distribution (allele C and T) that indicates that there is a significant association between the allotype distribution and Oligozoospermia with p value of 0.005 (p<0.05). In conclusion, MTHFR gene polymorphism C677T is associated with the occurrence of Oligozoospermia in Indonesian men."

"Polimorfisme gen Pax9 yang telah dikenal sebagai gen yang bertanggung jawab terhadap terjadinya agenesis gigi. Penelitian terdahulu memperlihatkan adanya hubungan antara agenesis gigi dengan pertumbuhan skeletal maksila dan mandibula sehingga penelitian ini bertujuan untuk mengevaluasi asosiasi polimorfisme gen Pax9 rs8004560, rs2073245 dan rs2073246 terhadap Variasi Maloklusi Skeletal, Pertumbuhan Maksila dan Mandibula serta Agenesis Gigi. Penelitian cross-sectional dilakukan pada 150 pasien ortodontik RSKGM FKG UI dan diklasifikasikan berdasarkan maloklusi skeletal. Ekstraksi DNA dilakukan dengan sampel rambut yang kemudian genotyping dilakukan dengan polymerase chain reaction (PCR) dan Sanger Sequencing. Polimorfisme gen Pax9 rs2073245 dan rs2073246 konsisten dengan Hardy Weinberg Equilibrium. Asosiasi ditemukan pada polimorfisme Pax9 rs8004560 dengan agenesis gigi (p= 0.025, OR= 2.895, CI= 1.101-7.614). Tidak ditemukan asosiasi polimorfisme gen Pax9 pada studi ini dengan maloklusi skeletal.  Jumlah sampel yang lebih tinggi dengan sistem klusterisasi latar belakang etnis disarankan pada penelitian berikutnya untuk mendeterminasi peran gen Pax9 terhadap maloklusi skeletal pada subpopulasi Indonesia.

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Polymorphism Pax9 has been widely researched and known as a gene responsible for tooth agenesis, and recently been found associated with skeletal malocclusion. This study aimed to determine the association of gene polymorphism Pax9 rs8004560, rs2073245 and rs2073246 to skeletal malocclusion in Indonesia. Cross sectional study was performed to 150 Orthodontics patients and classified according to their skeletal malocclusion by cephalometric analysis. Genomic DNA was extracted from hair samples and then genotyped by polymerase chain reaction and Sanger sequencing. Gene polymorphism Pax9 rs2073245 and 2073246 are consistent with Hardy Weinberg Equilibrium. Significant association was found in polymorphism Pax9 rs8004560 with Tooth Agenesis (p= 0.025, OR= 2.895, CI= 1.101-7.614). There were no association between PAX9 polymorphisms assessed in this study with skeletal malocclusion. Our result suggested further research using larger sample size and clustered background ethnicity is required to determine the role PAX9 gene relate to skeletal malocclusion in Indonesian subpopulation."