November 2011, Vol. 40 No. 11 488 KCNQ1 Variants Associate with Type 2 Diabetes in Malaysian Malay Subjects Riyadh Saif-Ali, 1,2 PhD, Sekaran Muniandy, 1 PhD, Zaid Al-Hamodi, 1 MSc, Cheng Siang Lee, 1 MSc, Khaled A Ahmed, 1 PhD, Abdulsalam M Al-Mekhlai, 3 MSc, Ikram Shah Ismail, 4 PhD, MRCP, MBBS Introduction Diabetes is the most common metabolic disease that affects 246 million people worldwide. The International Diabetes Federation (IDF) predicts that the total number of people living with diabetes will increase to 380 million within the next 20 years. 1 Diabetes, mostly type 2 diabetes mellitus (T2D), now affects 5.9% of the world’s adult population, with almost 80% of patients originating from developing countries. 2 More than 1.3 million Malaysians have diabetes and the IDF has predicted that this number would be doubled by 2025. A new approach known as genome-wide association (GWAS) study has been applied to complex diseases including T2D and has resulted in the identiication of a growing number of trait susceptibility loci for T2D. 3 Two independent GWAS studies have identiied a novel T2D Abstract Introduction: Type 2 diabetes (T2D) candidate gene: potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) was suggested by conducting a genome wide association study (GWAS) in Japanese population. Association studies have been replicated among East Asian populations; however, the association between this gene and T2D in Southeast Asian populations still needs to be studied. This study aimed to investigate the association of KCNQ1 common variants with type 2 diabetes in Malaysian Malay subjects. Materials and Methods: The KCNQ1 single nucleotide polymorphisms (SNPs): rs2237892, rs2283228, and rs2237895 were genotyped in 234 T2D and 177 normal Malay subjects. Results: The risk allele of the rs2283228 (A) was strongly associated with T2D (OR = 1.7, P = 0.0006) while the rs2237892 (C) was moderately associated with T2D (OR = 1.45, P = 0.017). The recessive genetic models showed that rs2283228 was strongly associated with T2D (OR = 2.35, P = 0.00005) whereas rs2237892 showed a moderate association with T2D (OR = 1.69, P = 0.01). The haplotype block (TCA), which contained the protective allele, correlated with a protection from T2D (OR = 0.5, P = 0.003). Furthermore, the diplotype (CAA-TCA) that contained the protective haplotype was protected against T2D (OR = 0.46, P = 0.006). Conclusion: The KCNQ1 SNPs, haplotypes and diplotypes are associated with T2D in the Malaysian Malay subjects. Ann Acad Med Singapore 2011;40:488-492 Key words: Diplotypes, Haplotypes, KCNQ1, SNPs, Type 2 diabetes 1 Department of Molecular Medicine, Faculty of Medicine, University Malaya 2 Department of Biochemistry, Faculty of Medicine, Sana’a University, Yemen 3 Department of Parasitology, Faculty of Medicine, University Malaya 4 Department of Medicine, University Malaya medical Center, University Malaya, Malaysia Address for Correspondence: Riyadh Saif-Al, Protein Lab, Department of Molecular Medicine, Faculty of Medicine, University Malaya, 50603 Kuala Lumpur, Malaysia. Email: reyadh70@yahoo.com susceptibility gene: potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) in East Asian subjects. 4,5 Very recently, 2 GWAS studies on Chinese Han and European populations confirmed KCNQ1 as T2D susceptibility gene. 6,7 The association of T2D with KCNQ1 variants was replicated in studies among Chinese, 8-10 Singaporeans, 11,12 Indians 13 and in some Euro- Caucasians. 4,14,15 The KCNQ1 gene contains 16 exons and spans more than 404 kb on chromosome 11p15.5, and encodes the pore-forming alpha subunit of the voltage-gated K+ channel (KvLQT1) which plays an important role in controlling the repolarisation process of the ventricles. 16,17 KCNQ1 is ubiquitously expressed in epithelial cells, including the endocrine and exocrine pancreas. 18 KCNQ1 was reported KCNQ1 Associate with T2D in Malays—Riyadh Saif-Ali et al Original Article