PMID- 27111895 OWN - NLM STAT- MEDLINE DCOM- 20170327 LR - 20221207 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 4 DP - 2016 TI - Association of DPP4 Gene Polymorphisms with Type 2 Diabetes Mellitus in Malaysian Subjects. PG - e0154369 LID - 10.1371/journal.pone.0154369 [doi] LID - e0154369 AB - BACKGROUND: Genetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4) gene may play a role in the etiology of type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV). METHOD: Ten DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 controls. Of these, 71 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. The odds ratios (ORs) and their 95% confidence interval (CIs) were calculated using multiple logistic regression for the association between the SNPs of DPP4 and T2DM. In addition, the serum levels of sDPP-IV were investigated to evaluate the association of the SNPs of DPP4 with the sDPP-IV levels. RESULTS: Dominant, recessive, and additive genetic models were employed to test the association of DPP4 polymorphisms with T2DM, after adjusting for age, race, gender and BMI. The rs12617656 was associated with T2DM in Malaysian subjects in the recessive genetic model (OR = 1.98, p = 0.006), dominant model (OR = 1.95, p = 0.008), and additive model (OR = 1.63, p = 0.001). This association was more pronounced among Malaysian Indians, recessive (OR = 3.21, p = 0.019), dominant OR = 3.72, p = 0.003) and additive model (OR = 2.29, p = 0.0009). The additive genetic model showed that DPP4 rs4664443 and rs7633162 polymorphisms were associated with T2DM (OR = 1.53, p = 0.039), and (OR = 1.42, p = 0.020), respectively. In addition, the rs4664443 G>A polymorphism was associated with increased sDPP-IV levels (p = 0.042) in T2DM subjects. CONCLUSIONS: DPP4 polymorphisms were associated with T2DM in Malaysian subjects, and linked to variations in sDPP-IV levels. In addition, these associations were more pronounced among Malaysian Indian subjects. FAU - Ahmed, Radwan H AU - Ahmed RH AD - Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. FAU - Huri, Hasniza Zaman AU - Huri HZ AD - Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. AD - Clinical Investigation Centre, University Malaya Medical Centre, Kuala Lumpur, Malaysia. FAU - Al-Hamodi, Zaid AU - Al-Hamodi Z AD - Department of Biochemistry and Molecular Biology, Faculty of Medicine, Sana'a University, Sana'a, Yemen. FAU - Salem, Sameer D AU - Salem SD AD - Department of Biochemistry and Molecular Biology, Faculty of Medicine, Sana'a University, Sana'a, Yemen. FAU - Al-Absi, Boshra AU - Al-Absi B AD - Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. FAU - Muniandy, Sekaran AU - Muniandy S AD - Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160425 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (CTLA-4 Antigen) RN - 0 (CTLA4 protein, human) RN - EC 3.4.14.5 (DPP4 protein, human) RN - EC 3.4.14.5 (Dipeptidyl Peptidase 4) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Alleles MH - Asian People MH - CTLA-4 Antigen/genetics MH - Child MH - Child, Preschool MH - Diabetes Mellitus, Type 2/*ethnology/*genetics MH - Dipeptidyl Peptidase 4/*genetics MH - Female MH - Genotype MH - Graves Disease/epidemiology/genetics MH - Haplotypes MH - Hashimoto Disease/epidemiology/genetics MH - Humans MH - Malaysia MH - Male MH - Middle Aged MH - Polymorphism, Genetic MH - *Polymorphism, Single Nucleotide MH - Young Adult PMC - PMC4844141 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2016/04/26 06:00 MHDA- 2017/03/28 06:00 PMCR- 2016/04/25 CRDT- 2016/04/26 06:00 PHST- 2016/01/20 00:00 [received] PHST- 2016/04/12 00:00 [accepted] PHST- 2016/04/26 06:00 [entrez] PHST- 2016/04/26 06:00 [pubmed] PHST- 2017/03/28 06:00 [medline] PHST- 2016/04/25 00:00 [pmc-release] AID - PONE-D-16-02705 [pii] AID - 10.1371/journal.pone.0154369 [doi] PST - epublish SO - PLoS One. 2016 Apr 25;11(4):e0154369. doi: 10.1371/journal.pone.0154369. eCollection 2016.