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

• Published in: 世界糖尿病杂志：英文版（电子版） no. 2; pp. 358 - 366
• Main Author: 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
• Format: Journal Article
• Language: English
• Published: 2015
• Subjects: Casecontrol;Association; diabetes; Gene; Genetics; Oman; Type; Variants
• ISSN: 1948-9358; 1948-9358

AIM： 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 highestgenotype variation % between diabetics and controlswas found at KCNJ11 （2.07%） and TCF7L2 （1.62%）.This study was not able to detect an association ofT2D risk with gene variants of IGF2BP2 （rs4402960）,SLC30A8 （rs13266634）, CAPN10 （rs3792267） andHHEX （rs1111875）. Moreover, no association wasfound between FTO gene variants （rs9939609 andrs8050136） and T2D risk. However, T2D risk was foundto be significantly associated with obesity （P = 0.002,OR = 2.22）; and with the Waist-to-Hip ratio （n = 532, P= 1.9 ×10^-7, OR = 2.4）, [among males （n = 234, P = 1.2× 10^-4, OR = 2.0） and females （n = 298, P = 0.001, OR= 6.3）].CONCLUSION： Results confirmed the associationof KCNJ11 （rs5219）, TCF7L2 （rs7903146）, CDKAL1（rs10946398） and CDKN2A/B （rs10811661） gene variantswith susceptibility to T2D among Omani Arabs.