VARIANT OF TRANSCRIPTION FACTOR 7 LIKE 2 (TCF7L2) GENE AS TYPE-2 DIABETES MELLITUS MARKER IN ETHNIC MINANGKABAU

• Main Author: Badriyya, Elsa
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/47158
• Institution: Institut Teknologi Bandung

Type 2 Diabetes Mellitus (T2DM) is a degenarative disease characterized by elevated glucose levels in the blood (hyperglicemia) resulting from defects in insulin secretion, insulin action, or both. Patients with T2DM commonly suffer from macrovascular and microvascular complication that can cause death. The prevalence of T2DM has been increasing rapidly in developed and developing countries including Indonesian. Province in Indonesian which has high prevalence of T2DM is West Sumatera. Variant of Transcription Factor 7 Like 2 (TCF7L2) gene rs11196205, rs4506565, and rs7901695 has been associated with T2DM in several regions like South asian, Danish, Saudi arabia, Malaysia and Thailand. TCF7L2 gene encodes a high mobility group box–containing transcription factor that plays a key role in the Wnt signaling pathway. TCF7L2 gene has a role to regulate the production of incretin hormone. The aim of this research was to identified SNP rs11196205, rs4506565, and rs7901695 of TCF7L2 gene and to find an association between that variants with T2DM in ethnic Minangkabau. Design of study was a case control study included 62 T2DM patients who came for treatment to the Metabolic Endocrinology Polyclinic at Dr. M. Jamil Hospital and 62 healthy controls who match with the inclusion and exclusion criteria. PureLink Genomic DNA kits was used to extract DNA from blood sample. Testing for effectivity of genomic isolation was by electrophoresis on agarose gel 1.5%. Tetra-primer Amplification Refractory Mutation System Polimerase Chain Reaction (ARMS PCR) was used for identifying TCF7L2 rs11196205, rs 4506565 and rs7901695 gene polymorphisms. Primer were constructed using Geneious program. The TCF7L2 gene sequence used for primer construction was obtained from the NCBI gene bank. The success of an ARMS PCR is highly dependent on the specificity of the constructed primer. Electrophoresis agarose was used to detect the ARMS PCR DNA amplification product. For identification SNP rs11196205, a sample with allele C produced specific fragments of 559 bp, and sample with allele G produced specific fragments of 339 bp. Meanwhile for identification SNP rs4506565, a sample with allele T and A produced specific fragment of 271 bp and 417 bp, respectively. Sample with allele T and C produced specific fragment of 177 bp and 367 bp for identified SNP rs7901695. Data was analyzed with Chi-square and Fisher’s exact test. Based on the research,genotype GC of SNP rs11196205 (p=0.047), genotype TC of rs7901695 (p=0.014), combination of rs11196205 and rs4506565 GC-TA (p=0.021) along with the combination of all SNP GC-TA-TC (p=0.032) were significantly associated to T2DM. Therefore, SNP rs11196205, rs7901695, combination of rs11196205 and rs4506565 along with the combination of all SNP TCF7L2 gene can be used as genetic marker of T2DM in ethnic Minangkabau.