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"Respon wanita usia reproduksi bervariasi terhadap stimulasi FSH eksogen. Salah satu penyebab variasi tersebut adalah perbedaan genotip akibat adanya polimorfisme pada ekson 10 gen reseptor FSH. Untuk mengetahui lebih lanjut apakah daerah promotor inti gen reseptor FSH juga polimorfik dan apakah polimorfisme tersebut mempengaruhi aktivitas promotor, dilakukan skrining polimorfisme promotor gen reseptor FSH pada 262 wanita yang mengikuti program IVF/ICSI, diikuti uji fungsional untuk mengetahui pengaruh polimorfisme terhadap aktivitas promotor. Hasil penelitian menunjukkan bahwa daerah promotor inti gen reseptor FSH polimorfik. Ditemukan lima SNPs pada posisi –29, –37, –114, –123 dan –138 di samping ditemukannya variasi jumlah basa adenin. Polimorfisme pada posisi –123 menurunkan aktivitas promotor secara bermakna, sebaliknya polimorfisme pada posisi –37 dan –138 meningkatkan aktivitas promotor secara bermakna, sedangkan polimorfisme pada posisi –29, –114 dan pemendekan basa adenin tidak mempengaruhi aktivitas promotor secara bermakna. Perbedaan aktivitas promotor akibat polimorfisme ini pada akhirnya sangat memungkinkan merubah sensitivitas ovarium terhadap FSH. (Med J Indones 2004; 13: 205-14)

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Women of reproductive ages are varies in their responses to exogenous FSH stimulations. The difference of FSHR genotype due to the polymorphisms in exon 10 is one of its significant factors. To know further whether the core promoter of FSHR is also polymorphic and to know whether those polymorphisms influence the promoter activity, we did polymorphism screening of FSHR promoter to 262 women undergoing IVF/ICSI, followed by functional study to know the impact of polymorphisms to the promoter activity. This study indicated that the core promoter of human FSHR is polymorphic. We found five SNPs at positions –29, –37, –114, –123 and –138 in addition to the variety number of adenines. Polymorphism at position –123 significantly decreased the promoter activity, in contrast, polymorphism at position –37 and –138 significantly increased the promoter activity, whereas polymorphism at position –29, –114 and short adenines stretch did not significantly influence the promoter activity. The differences of the promoter activities due to polymorphisms might change the ovarian sensitivity to FSH. (Med J Indones 2004; 13: 205-14)"

"Latar Belakang: Faktor transkripsi Hypoxia inducible factor-1 (HIF-1 merupakanpengatur utama hipoksia, termasuk menyebabkan penekanan sistem perbaikan deoxyribose nucleic acid (DNA), sehingga menghasilkan instabilitas genetik pada sel kanker. Varian genetik HIF-1α C1772T (P582S) dan G1790A (A588T) dipercaya mempunyai aktivitas transkripsi yang lebih tinggi.Peranan polimorfisme HIF-1α ini sudah diteliti pada beberapa jenis kanker seperti kanker ginjal, payudara, ovarium, tetapi belum ada penelitian pada kanker paru. Metode: Polimorfisme HIF-1α diperiksa dengan menggunakan direct sequencing dengan total sampel 83 pasien kanker paru (42 adenokarsinoma, 30 skuamous sel karsinoma, empat adenoskuamous sel karsinoma dan tujuh kanker paru karsinoma sel kecil (KPKSK) dan 110 subjek sehat sebagai kontrol. Hubungan polimorfisme HIF-1α dengan kelainan genetik/epigentik loss of heterozygot (LOH) TP53, LOH 1p34, LOH retinoblastoma-1 (RB1), inaktivasi p16 dan kelainan epidermal growth factor receptor (EGFR) kemudian diperiksa. Hasil: Frekuensi polimorfisme HIF-1α pada kanker paru dan kontrol telah sesuai dengan keseimbangan Hardy-Weinberg. Pada penelitian ini tidak ditemukan perbedaan frekuensi genotipe C1772T atau G1790A antara kanker paru dengan kontrol sehat. Tetapi, frekuensi varian HIF1A C1772T ditemukan tinggi bermakna di pasien kanker paru dengan LOH TP53 (p=0,015). Pada pasien adenokarsinoma, individu dengan varian alel memiliki frekuensi tinggi LOH TP53 (p=0,047), LOH 1p34 (p=0,009) atau keduanya (LOH TP53 dan LOH 1p34) (p=0,008). Aktivitas transkripsi juga diperiksa secara in vitro dan ditemukan HIF1A varian pada sel kanker paru A549 mempunyai aktivitas yang meningkat secara bermakna dibanding wild type HI1F1A baik di kondisi normoksia atau hipoksia, terutama P582A di sel dengan mutan p53 (p< 0,0005 dan p< 0,005). Kesimpulan: Penelitian ini mengindikasikan polimorfisme gen HIF-1α mempunyai peranan penting dalam karsinogenesis paru terutama pada adenokarsinoma, diduga melalui peningkatan instabilitas genetik.

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Background and objective: The transcription factor, hypoxia-inducible factor-1 (HIF-1), is a master regulator of hypoxia, including repression of DNA repair systems, resulting in genomic instability in cancer cells. The roles of the polymorphic HIF-1a variants, C1772T (P582S) and G1790A (A588T), which are known to enhance transcriptional activity, were evaluated in lung cancers.

Methods: HIF-1a polymorphisms were assessed by direct sequencing in a total of 83 lung cancer patients (42 adenocarcinomas, 30 squamous cell, four adenosquamous cell and seven small cell lung carcinomas) and in 110 healthy control subjects. The relationship between these polymorphisms and the frequently observed genetic and/or epigenetic aberrations, TP53 loss of heterozygosity (LOH), 1p34 LOH, retinoblastoma-1 (RB1) LOH, p16 inactivation and epidermal growth factor receptor aberrations, was then assessed.

Results: There were no significant differences in genotype frequencies for either C1772T or G1790A between lung cancer patients and healthy controls. However, the frequency of the HIF1A C1772T variant allele was significantly higher in lung cancer patients with TP53 LOH (P = 0.015). Among adenocarcinoma patients, individuals with variant alleles of either polymorphism showed significantly higher frequencies of TP53 LOH (P = 0.047), 1p34 LOH (P = 0.009), or either of these (P = 0.008) in the tumours. The in vitro transcriptional activity of these HIF1A variants in A549 lung cancer cells was significantly greater than that of the wild type under either normoxic or hypoxic conditions, especially for P582S in cells containing mutant p53 (P < 0.0005 and P < 0.005, respectively).

Conclusions: These findings indicate that functional polymorphisms in the HIF-1a gene may have an important impact on lung carcinogenesis, especially in adenocarcinomas, possibly by increasing genomic instability."

"Endometriosis adalah kelainan ginekologis yang ditandai dengan adanya jaringan endometrium yang tumbuh di luar uterus. Penyakit ini bersifat multifaktorial, salah satunya dipengaruhi genetik. Polimorfisme genetik gen reseptor progesteron (PR) diketahui berhubungan dengan penyakit endometriosis. Penelitian ini bertujuan untuk mengetahui hubungan antara polimorfisme gen PR rs544843047 di bagian promoter dengan endometriosis di Indonesia. Penelitian ini menggunakan desain cross sectional, dengan membandingkan 25 jaringan endometriosis dari wanita penderita endometriosis dan 21 jaringan endometrium dari wanita tanpa endometriosis. Molekul DNA dari kedua jenis jaringan diisolasi, diamplifikasi dengan menggunakan metode PCR. Analisis perubahan nukleotida pada gen PR dilakukan dengan metode sequencing. Hasil penelitian menunjukkan frekuensi genotip dan alel pada SNP gen PR rs544843047 adalah genotip TT 100% dan alel T 100%. Penelitian ini menyimpulkan bahwa tidak ada hubungan antara SNP gen PR pada rs544843047 dengan penyakit endometriosis di Indonesia.

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Endometriosis is a gynecological disorder characterized by the presence of endometrial tissues that grow outside the uterus. This disease is multifactorial cause, one of which is influenced by genetics factor, and genetic polymorphism of the Progesterone Receptor (PR) gene is known to be associated with endometriosis. The aim of this study was to determine the relationship between PR gene polymorphism rs544843047 in the promoter and endometriosis in Indonesia. A cross sectional design was used in this study, comparing 25 endometriosis tissues of women with endometriosis and 21 endometrial tissues of women without endometriosis. DNA molecules from both types of tissues were isolated, then amplified using the PCR method. While analysis of nucleotide changes in the PR gene was conducted by sequencing. The results showed that the genotypic and allelle frequencies of the PR rs544843047 SNP were 100% TT genotype and 100% T allele. This research concludes that there are no association between SNP PR gene in rs544843047 and endometriosis in Indonesia."

"Dalam beberapa tahun terakhir, beberapa penelitian telah membuktikan bahwa variasi genetik berkontribusi terhadap kesehatan fisik dan mental manusia serta mempengaruhi hasil terapinya. Sejumlah penelitian juga telah menyelidiki peran Single Nucleotide Polymorphisms (SNP) dalam farmakodinamik dan farmakokinetik kemoterapi seperti fluoropyrimidine, meskipun implementasi hasil yang diperoleh masih sederhana. Pada akhir tahun 2019, WHO menemukan kasus pneumonia baru yang disebabkan oleh Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2), yang kemudian dinyatakan sebagai pandemi coronavirus disease 2019 (COVID-19). Regulasi virus dipengaruhi oleh gen Angiotensin Converting Enzyme (ACE) dan Renin-Angiotensin System (RAS). Tujuan dari penelitian ini adalah untuk melakukan uji coba deteksi SNP menggunakan protokol real-time quantitative Polymerase Chain Reaction (qPCR) dengan rhAmp SNP genotyping system pada rs4343. SNP rs4343 terletak di ekson 17 gen ACE dengan alel G dan A. Sampel darah diperoleh dari penyintas COVID-19 dan DNA genom diekstraksi dari sampel darah. Penelitian ini menggunakan fragmen gen gBlocks™ sebagai kontrol positif dan campuran qPCR terdiri dari rhAmp Master Mix, rhAmp Reporter Mix, dan rhAmp rs4343 assay. Hasil disajikan dalam bentuk plot allelic discrimination dan memberikan hasil yang kurang memuaskan untuk deteksi rs4343. Hanya 27 sampel terdeteksi memiliki alel G homozigot dari 50 sampel yang diuji dimana 23 sampel lainnya tidak berhasil dideteksi.

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In recent years, several studies have shown that genetic variation contributes to both the physical and mental health of humans and affects the outcome of therapy. A number of studies have also been carried out on the role of Single Nucleotide Polymorphisms (SNP) in the pharmacodynamics and pharmacokinetics of chemotherapy such as fluoropyrimidines, although the implementation of the results obtained is yet simple. At the end of 2019, WHO found a new case of pneumonia caused by Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2), which was later declared a pandemic coronavirus disease 2019 (COVID-19). The regulation of the virus was influenced by the Angiotensin Converting Enzyme (ACE) and Renin-Angiotensin System (RAS) genes. The aim of this study was to carry out a SNP detection trial employing a protocol of a real-time quantitative Polymerase Chain Reaction (qPCR) performing rhAmp SNP genotyping assay on rs4343. SNP rs4343 is located in exon 17 of the ACE gene with alleles G and A. Blood samples were obtained from COVID-19 survivors and the genomic DNAs were extracted from them. This study used gene fragment gBlocksTM as the positive control and the qPCR mix consisted rhAmp Master Mix, rhAmp Reporter Mix, and rhAmp rs4343 assay. The results were presented in the form of allelic discrimination plots and is not satisfied to use the method to detect rs4343.There are only 27 samples were detected to have the homozygous G allele out of 50 samples where the other 23 samples were undetermined."

"Latar belakang: Periodontitis adalah penyakit kronis terlokalisasi pada jaringan penyangga gigi. Penyebab penyakit ini multifaktorial, termasuk faktor genetik.Tujuan: Menganalisis hubungan polimorfisme genetik IL-10 pada laki-laki terhadap derajat keparahan periodontitis.Metode: Menggunakan tehnik PCR dan RFLP (enzim RSA I), dianalisis dengan elektroforesis dan divisualisasi menggunakan Gel Doc.Hasil: 44 sampel normal terdapat genotip: CC 27,27%, CA 41,37%, AA 11,36%; 70 kelompok periodontitis : ringan CC 50%, CA 12,5%, AA 37,5%; sedang: CC 38,9%, CA 47,2%, AA 13,9%; berat: CC 42,3%, CA 30,8%, AA 19,4%.Kesimpulan: Ditemukan gambaran polimorfisme IL-10 pada pada penelitian ini, namun tidak berhubungan dengan derajat keparahan periodontitis.(p>0.05).

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Background: Periodontitis is a chronic disease localized to the supporting tissue and bone of teeth. It is multifactorial, including genetic factors.

Aim: To analyze the relationship of genetic polymorphisms in the IL-10 men against the severity of periodontitis.

Methods: Using PCR and RFLP techniques (RSA enzyme I), were analyzed by electrophoresis and visualized using the Gel Doc.

Results: 44 normal samples contained genotypes: CC 27.27%, 41.37% CA, AA 11.36%; 70 samples of periodontitis: a light CC 50%, CA 12.5% ​​AA 37.5%; were: CC 38.9%, CA 47.2%, AA 13.9%, by weight: 42.3% CC, CA 30.8%, 19.4% AA.

Conclusion: We found the distribution of the IL-10 genetic polymorphism in the normal group and periodontitis groups, but not related to the severity of periodontitis. (P> 0.05)."

"Pendahuluan: Artesunat amodiakuin (AS-AQ) merupakan artemisinin-based combination therapy (ACT) yang digunakan sebagai lini pertama di berbagai daerah endemik di Indonesia. Studi sebelumnya pada pasien malaria falsiparum tanpa komplikasi di Sumba Indonesia menunjukkan gagal terapi sebesar 11,1%. Diduga salah satu penyebab kegagalan terapi adalah polimorfisme gen sitokrom P450 2C8 (CYP2C8), CYP1A1 dan CYP1B1. Penelitian ini bertujuan untuk mempelajari peran polimorfisme pada gen pemetabolisme artesunat amodiakuin terhadap kegagalan terapi amodiakuin. Metodologi: Analisis polimorfisme CYP2C8*2, CYP2C8*3, CYP1A1*2, CYP1B1*2 dan CYP1B1*3 dilakukan pada pasien malaria falsiparum yang mendapatkan AS-AQ di Sumba Indonesia (N=110). Single nucleotide polymorphisms (SNPs) dianalisis menggunakan polymerase chain reaction (PCR) dilanjutkan dengan retriction-fragment length polymorphism (RFLP) dan sekuensing. Hasil: Tidak ditemukan alel CYP2C8*2 dan alel CYP2C8*3 pada sampel penelitian (N=110). Frekuensi alel CYP1A1*2, CYP1B1*2 dan CYP1B1*3 berturut-turut sebanyak 5%, 23,6% dan 4,1%. Tidak ditemukan kemaknaan pada analisis haplotipe CYP1B1*2 (p=0,13, 95% CI: 0,11 – 1,34) dan CYP1B1*3 (p=0,34, 95% CI: 0,44 – 11,34). Hanya ditemukan tipe heterozigot pada alel CYP1A1*2 dan CYP1B1*3. Kesimpulan: Tidak ditemukan hubungan antara alel CYP2C8*2, CYP2C8*3, CYP1A1*2, CYP1B1*2 dan CYP1B1*3 dengan kegagalan terapi amodiakuin di Sumba, Indonesia.

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Introduction: Artesunate amodiaquine (AS-AQ) is one of the ACT used in many endemic areas in Indonesia. Previous study in Sumba showed that there were 11,1% treatment failure with AS-AQ in uncomplicated malaria falciparum patients. Polymorphisms in cytochrome P450 2C8 (CYP2C8), CYP1A1 and CYP1B1 genes are thought to be the major factors in the treatment failure of amodiaquine. The aim of this study was to analyze the role of polymorphisms in the genes encoding amodiaquine metabolizing enzymes (CYP2C8, CYP1A1, CYP1B1) in the treatment failure of amodiaquine.

Methodology: Polymorphisms of CYP2C8*2, CYP2C8*3, CYP1A1*2, CYP1B1*2 and CYP1B1*3 were studied in patients with malaria falciparum treated with AS-AQ in Sumba Indonesia (N=110). Single nucleotide polymorphisms (SNPs) were analyzed using polymerase chain reaction (PCR) continued with restriction-fragment length polymorphism (RFLP) and sequencing.

Results: There were no CYP2C8*2 and CYP2C8*3 alleles found in the samples (N=110). The frequency of CYP1A1*2, CYP1B1*2 and CYP1B1*3 alleles were 5%, 23,6% and 4,1%, respectively. There were no significant difference in haplotype analysis of CYP1B1*2 (p value=0,13, 95% confidence interval=0,11 – 1,34) and CYP1B1*3 (p value=0,34, 95% confidence interval=0,44 – 11,34). Heterozygote types were found in CYP1A1*2 and CYP1B1*3 alleles.

Conclusions: There were no associations between CYP2C8*2, CYP2C8*3, CYP1A1*2, CYP1B1*2 and CYP1B1*3 alleles with treatment failure of amodiaquine in Sumba, Indonesia."

"Reseptor follicle-stimulating hormone (FSHR) hanya terekspresi pada sel granulosa ovarium dan sel Sertoli testis. Ekspresinya yang sangat spesifik menunjukkan adanya peristiwa-peristiwa traskripsi khusus pada kedua tipe sel tersebut yang bertanggung jawab untuk aktivasi gen reseptor FSH. Walaupun mekanismenya belum diketahui, namun telah dicapai beberapa kemajuan menyangkut mekanisme yang mengontrol proses transkripsi dan regulasi gen reseptor FSH. Sampai saat ini telah diidentifikasi beberapa elemen regulator penting yang bertanggung jawab untuk proses transkripsi gen reseptor FSH yang tidak mengandung TATA box tersebut seperti elemen E box (CACG(A)TG, –124/–119), elemen GATA (TATC, –88/–85), E2F (TTTCGCG, –45/–39), dan elemen regulator-3 (–197/–171). Studi fungsional menunjukkan bila mutasi terjadi pada elemen regulator tersebut akan menurunkan fungsi promoter secara bermakna dan dampak terbesar terdeteksi bila mutasi terjadi pada elemen E box. Metilasi pada situs CpG spesifik dalam daerah promoter inti tampaknya memegang peranan penting dalam regulasi transkripsi gen reseptor FSH tikus dan mencit. (Med J Indones 2003; 12: 187-93)

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Follicle-stimulating hormone receptor (FSHR) is exclusively expressed in granulose cells of the ovary and Sertoli cells of the testis. The highly cell-specific of gene expression revealed that transcriptional events unique to these two cell types are responsible for activation of the FSHR gene. Even though its mechanisms are still unclear, several progress regarding the mechanism that control its basal transcription and regulation has been made. It has been identified several important elements that responsible for the transcription of the TATA-less FSHR gene such as: E box element (CACG(A)TG, –124/–119), an inverted GATA (TATC, –88/–85), E2F (TTTCGCG, –45/–39), and regulator element-3 (–197/–171). The functional studies shown that mutations through these regulatory elements significantly decrease the promoter function with greatest impact detected when mutation was done in E-box element. The site-specific CpG methylation within the core promoter seems play an important role in the regulation of rat and mouse FSHR gene expression. (Med J Indones 2003; 12: 187-93)"

"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."