Polimorfisme Gen Sterol Regulatory Element Binding Transcription Factor 1 rs2297508 sebagai Faktor Risiko Terjadinya Diabetes Melitus Tipe 2 pada Etnis Bugis

Farda Tsaqouva Ahza, Dr. Pramudji Hastuti, Apt.,MS; dr. Ahmad Hamim Sadewa, Ph.D

2023 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar Belakang: Prevalensi diabetes melitus diprediksi akan terus meningkat hingga 3 kali lipat secara global termasuk di Indonesia. Peningkatan prevalensi ini dapat meningkatkan risiko terjadinya komplikasi dan berujung pada kematian dini. Variasi genetik pada gen SREBF1 (Sterol Regulatory Element Binding Transcription Factor 1) rs2297508 (substitusi C>G) diketahui menjadi salah satu faktor yang dapat mempengaruhi kejadian DMT2 pada berbagai populasi. Tujuan: Penelitian ini bertujuan untuk menganalisis hubungan polimorfisme gen SREBF1 rs2297508 sebagai faktor risiko terjadinya Diabetes Melitus Tipe 2 pada etnis Bugis di Sulawesi Tengah. Metode: Penelitian observasional dengan desain case control. Sampel yang digunakan merupakan sampel whole blood dari subjek etnis Bugis yang tinggal di Sulawesi Tengah. Sebanyak 200 subjek dikelompokkan menjadi 2 kelompok, yaitu kelompok DMT2 dan kelompok kontrol. Subjek dinyatakan DMT2 apabila memiliki kadar GDP > 125 mg/dL dan atau HbA1c > 6,4%. Pengukuran GDP dilakukan dengan metode GOD-PAP, sedangkan HbA1c diukur menggunakan HPLC. Analisis genotip dilakukan dengan metode PCR-RFLP. Analisis bivariat dan multivariat digunakan untuk mengetahui hubungan antara polimorfisme gen SREBF1 rs2297508 dengan kejadian DMT2. Hasil: Frekuensi genotip GG dan gabungan genotip CG+GG pada kedua kelompok lebih tinggi dibandingkan genotip CC. Alel G meningkatkan risiko DMT2 pada keseluruhan subjek (OR = 1,365; 95% CI = 1,161-3,168; nilai p = 0,045) dibanding dengan genotip CC. Rerata kadar HbA1c dan GDP pada genotip GG lebih tinggi dibanding genotip CG dan CC. Analisis multivariat menunjukkan bahwa polimorfisme gen SREBF1 rs2297508 berkaitan dengan risiko DMT2 pada kedua populasi setelah dikendalikan dengan variabel IMT, usia, jenis kelamin dan obesitas sentral. Kesimpulan: Individu dengan genotip CG+GG dan alel G polimorfisme gen SREBF1 rs2297508 berperan dalam meningkatkan risiko terjadinya DMT2 dibanding individu dengan genotip CC dan alel C.

Background: The prevalence of diabetes mellitus is predicted to rise threefold globally, including in Indonesia. The increasing prevalence can lead to a higher risk of complications and premature death. Genetic variation in SREBF1 (Sterol Regulatory Element Binding Transcription Factor 1) gene rs2297508 (C>G substitution) is known to be one of the factors that can affect the incidence of T2DM in various populations. Objective: This study aims to analyze the relationship between the polymorphism SREBF1 gene rs2297508 as a risk factor for Type 2 Diabetes Mellitus in the Buginese Tribe in Central Sulawesi. Methods: Observational research with a case-control design. The samples used were whole blood samples from Buginese tribe subjects living in Central Sulawesi. A total of 200 subjects were grouped into 2 groups, which were the T2DM group and the control group. Subjects were categorized as having T2DM if they had GDP > 125 mg/dL and or HbA1c > 6.4%. GDP was measured using the GOD-PAP method, while HbA1c was measured using HPLC. Genotyping analysis was performed using the PCR-RFLP method. Bivariate and multivariate analyses were used to determine the association between polymorphism SREBF1 gene rs2297508 and T2DM incidence. Results: The frequency of the GG genotype and the combined CG+GG genotype in both groups was higher than the CC genotype. The G allele increased the risk of T2DM in all subjects (OR = 1.365; 95% CI = 1.161-3.168; p value = 0.045) compared to the C allele. Mean HbA1c and GDP levels in the GG genotype were higher than those in the CG and CC genotypes. Multivariate analysis showed that the polymorphism SREBF1 gene rs2297508 was associated with T2DM risk in both populations after controlling for BMI, age, gender, and central obesity variables. Conclusion: Individuals with the CG+GG genotype and G allele of the polymorphism SREBF1 gene rs2297508 contribute to an increased risk of T2DM compared to individuals with the CC genotype and C allele

Kata Kunci : HbA1c, Type 2 Diabetes Mellitus, SREBF1 gene, rs2297508