Case Control Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2015; 6(2): 358-366
Published online Mar 15, 2015. doi: 10.4239/wjd.v6.i2.358
Association of gene variants with susceptibility to type 2 diabetes among Omanis
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
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, Riad Bayoumi, Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Sultanate of Oman
Yengo Loic, Philippe Froguel, Genomics and Metabolic Disease, CNRS UMR8199, 59045 Lille Cedex, France
Yengo Loic, Philippe Froguel, Institute Pasteur of Lille, Lille2 University, 59000 Lille, France
Author contributions: Al-Sinani S and Bayoumi R performed the majority of design and experiments; Al-Sinani S, Woodhouse N, Al-Mamari A, Al-Shafie O and Al-Shafaee M helped in patients selection and samples collection; Al-Sinani S, Woodhouse N, Al-Mamari A, Al-Shafie O, Al-Shafaee M, Al-Yahyaee S, Hassan M, Jaju D, Al-Hashmi K, Al-Abri M, Al-Rassadi K and Bayoumi R designed the study and helped in writing the manuscript; Al-Sinani S, Rizvi S, Loic Y and Froguel P helped in statistical analysis.
Supported by The Research Council (TRC), Muscat, Oman, No. RC/MED/BIOC/10/01.
Ethics approval: The study was approved by the Ethics and Research Committee of the College of Medicine, Sultan Qaboos University, Muscat, Oman.
Informed consent: All involved persons gave their informed consent written prior to study inclusion.
Conflict-of-interest: The authors declare that they have no conflicts of interest concerning this article.
Data sharing: No.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Sawsan Al-Sinani, PhD Biochemistry, Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, PO Box-35, Muscat 123, Sultanate of Oman. sawsan.alsinani@gmail.com
Telephone: +968-24-141113 Fax: +968-24-141114
Received: June 19, 2014
Peer-review started: June 20, 2014
First decision: July 18, 2014
Revised: November 20, 2014
Accepted: February 4, 2015
Article in press: February 9, 2015
Published online: March 15, 2015
Processing time: 272 Days and 21.5 Hours
Abstract

AIM: To investigate the association of 10 known common gene variants with susceptibility to type 2 diabetes mellitus (T2D) among Omanis.

METHODS: Using case-control design, a total of 992 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 relative with 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 ≥ 1.3 reaching 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 IGF2BP2 (rs4402960), SLC30A8 (rs13266634), CAPN10 (rs3792267) and HHEX (rs1111875). Moreover, no association was found between FTO gene variants (rs9939609 and rs8050136) and T2D risk. However, T2D risk was found to 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 association of KCNJ11 (rs5219), TCF7L2 (rs7903146), CDKAL1 (rs10946398) and CDKN2A/B (rs10811661) gene variants with susceptibility to T2D among Omani Arabs.

Keywords: Type 2 diabetes; Genetics; Oman; Case-control; Association; Gene; Variants

Core tip: To investigate the association of 10 known common gene variants with susceptibility to type 2 diabetes mellitus (T2D) among Omani Arabs using case-control design. A total of 992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped 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). Four gene variants showed significant association with T2D risk: KCNJ11 (rs5219), TCF7L2 (rs7903146), CDKAL1 (rs10946398) and CDKN2A/B (rs10811661). The highest genotype variation % between diabetics and controls was found at KCNJ11 and TCF7L2 gene variants.