ASSOCIATION STUDY OF POLYMORPHISMS OF 15 DIABETES-RELATED LOCI IDENTIFIED BY GENOME-WIDE ASSOCIATION SCANS WITH TYPE 2 DIABETES IN LEBANESE POPULATION

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 796-817-Diabetes Genetics & Epidemiology
Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-806
Wassim Y Almawi*1, Rita Fayez Nemr2, Akram Salim Echtay3, Fabiola Lisa Saldanha4 and Sose H Keleshian5
1Arabian Gulf Univ, Manama, Bahrain, 2UMCRH, Achrafieh, Beyrouth, Lebanon, 3Rafik Hariri Univ Hosp, Beirut, Lebanon, 4Arabian Gulf University, Manama, Bahrain, 5Haigazian University, Beirut, Lebanon
Background and aim. Recent genome-wide association scans (GWAS) and replication studies have expanded the list of validated type 2 diabetes (T2DM) susceptibility loci, with nearly 40 distinct T2DM susceptibility loci identified in European and Asian populations.  However, studies investigating GWAS-validated T2DM polymorphisms in Arab populations, including (East Mediterranean) Lebanese are limited. We aimed to replicate the T2DM association of 18 SNPs from 15 candidate loci, previously identified in Europeans, in Lebanese Arab population.

Methods. This was a case-control association study comprising 995 T2DM patients and 1,195 normoglycaemic control participants. We genotyped by allelic discrimination method 18 SNPs in or near ADAM30, NOTCH2, THADA, TMEFF2, COL8A1, ADAMTS9-AS2, WFS1, JAZF1, SLC30A8, KCNQ1, LOC387761, ALX4, TSPAN8, FTO, and HNF1, which were previously associated with T2DM in European populations.

Results.  The risk-allele frequencies of the tested SNPs were comparable with those reported for Caucasians. We demonstrated significant associations of COL8A1 rs792837 [P <0.001; OR(95% CI) = 1.45 (1.24-1.68)], KCNQ1 rs2237892 [P <0.001; OR(95% CI) = 2.53 (2.09-3.05)] and rs2237895 [P = 0.014; OR(95% CI) = 1.20 (1.04-1.38)], ALX4 rs729287 [P = 0.001; OR(95% CI) = 1.36 (1.13-1.65)], FTO rs8050136 [P = 0.039; OR(95% CI) = 1.16 (1.01-1.34)] and rs17817449 [P = 0.036; OR(95% CI) = 1.18 (1.01-1.37)], and HNF1 rs4430796 [P = 0.008; OR(95% CI) = 0.80 (0.68-1.95)] with T2DM, with similar effect sizes to those reported for European populations. Lack of association for the rest of the variants may have resulted from insufficient power to detect smaller allele effects.

Conclusions/interpretation. In addition to our previous findings demonstrating the association of IGF2BP2, CDKAL1, TCF7L2 and EXT2 variants with T2DM among Lebanese, here we extend these by validating the association of six additional established loci with T2DM in Lebanese Arabs.

Nothing to Disclose: WYA, RFN, ASE, FLS, SHK

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: THis work was supported by grants from AGU Research Funds