Association of gene variants with susceptibility to type 2 diabetes among Omanis  

作　　者：Sawsan Al-Sinani Nicolas Woodhouse Ali Al-Mamari Omaima Al-Shafie Mohammed Al-Shafaee Said Al-Yahyaee Mohammed Hassan Deepali Jaju Khamis Al-Hashmi Mohammed Al-Abri Khalid Al-Rassadi Syed Rizvi Yengo Loic Philippe Froguel Riad Bayoumi 

机构地区：[1]Department of Biochemistry, College of Medicine and Health Sciences,Sultan Qaboos University [2]Genomics and Metabolic Disease [3]Institute Pasteur of Lille, Lille2 University

出　　处：《World Journal of Diabetes》2015年第2期358-366,共9页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by The Research Council(TRC),Muscat,Oman,No.RC/MED/BIOC/10/01

摘　　要：AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped,by an allelic discrimination assay-by-design TaqMan method on fast real time polymerase chain reaction system,for the following gene variants:KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398),CDKN2A/B(rs10811661),FTO(rs9939609 and rs8050136),IGF2BP2(rs4402960),SLC30A8(rs13266634)CAPN10(rs3792267)and HHEX(rs1111875).T2D patients were recruited from the Diabetes Clinic(n=243)and inpatients(n=749)at Sultan Qaboos Univesity Hospital(SQUH),Muscat,Oman.Adult control participants(n=294)were volunteers from the community and from those visiting Family Medicine Clinic at SQU,for regular medical checkup.The difficulty in recruiting Omani participants with no family history of diabetes was the main reason behind the small number of control participants in this study.Almost all volunteers questioned had a relativewith diabetes mellitus.Inspite of the small number of normoglycemic controls in this study,this sample was sufficient for detection of genes and loci for common alleles influencing T2D with an odds ratio of≥1.3reaching at least 80%power.Data was collected from June 2010 to February 2012.RESULTS:Using binary logistic regression analysis,four gene variants showed significant association with T2D risk:KCNJ11(rs5219,P=5.8×10^(-6),OR=1.74),TCF7L2(rs7903146,P=0.001,OR=1.46),CDKAL1(rs10946398,P=0.002,OR=1.44)and CDKN2A/B(rs10811661,P=0.020,OR=1.40).The fixation index analysis of these four gene variants indicated significant genetic differentiation between diabetics and controls{[KCNJ11(rs5219),P<0.001],[TCF7L2(rs7903146),P<0.001],[CDKAL1(rs10946398),P<0.05],[CDKN2A/B(rs10811661),P<0.05]}.The highest genotype variation%between diabetics and controls was found at KCNJ11(2.07%)and TCF7L2(1.62%).This study was not able to detect an association of T2D risk with gene variants of IAIM： To investigate the association of 10 knowncommon gene variants with susceptibility to type 2diabetes mellitus （T2D） among Omanis.METHODS： Using case-control design, a total of992 diabetic patients and 294 normoglycemic OmaniArabs were genotyped, by an allelic discriminationassay-by-design TaqMan method on fast real timepolymerase chain reaction system, for the followinggene variants： KCNJ11 （rs5219）, TCF7L2 （rs7903146）,CDKAL1 （rs10946398）, CDKN2A/B （rs10811661）, FTO（rs9939609 and rs8050136）, IGF2BP2 （rs4402960）,SLC30A8 （rs13266634） CAPN10 （rs3792267） andHHEX （rs1111875）. T2D patients were recruited fromthe Diabetes Clinic （n = 243） and inpatients （n = 749）at Sultan Qaboos Univesity Hospital （SQUH）, Muscat,Oman. Adult control participants （n = 294） werevolunteers from the community and from those visitingFamily Medicine Clinic at SQU, for regular medicalcheckup. The difficulty in recruiting Omani participantswith no family history of diabetes was the main reasonbehind the small number of control participants in thisstudy. Almost all volunteers questioned had a relative with diabetes mellitus. Inspite of the small number ofnormoglycemic controls in this study, this sample wassufficient for detection of genes and loci for commonalleles influencing T2D with an odds ratio of ≥ 1.3reaching at least 80% power. Data was collected fromJune 2010 to February 2012.RESULTS： Using binary logistic regression analysis,four gene variants showed significant association withT2D risk： KCNJ11 （rs5219, P = 5.8 × 10^-6, OR = 1.74）,TCF7L2 （rs7903146, P = 0.001, OR = 1.46）, CDKAL1（rs10946398, P = 0.002, OR = 1.44） and CDKN2A/B（rs10811661, P = 0.020, OR = 1.40）. The fixation indexanalysis of these four gene variants indicated significantgenetic differentiation between diabetics and controls{[KCNJ11 （rs5219）, P 〈 0.001], [TCF7L2 （rs7903146）,P 〈 0.001], [CDKAL1 （rs10946398）, P 〈 0.05],[CDKN2A/B （rs10811661）, P 〈 0.05]}. The high

关 键 词：Type 2 DIABETES GENETICS Oman Casecontrol ASSOCIATION GENE VARIANTS 

分 类 号：R587.1[医药卫生—内分泌]