Association of DPP4 Gene Polymorphisms with Type 2 Diabetes Mellitus in Malaysian Subjects.
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).



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.



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.



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.
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Radwan H
RH
Ahmed
Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Clinical Investigation Centre, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
Hasniza Zaman
HZ
Huri
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Sana'a University, Sana'a, Yemen.
Zaid
Z
Al-Hamodi
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Sana'a University, Sana'a, Yemen.
Sameer D
SD
Salem
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Boshra
B
Al-Absi
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Sekaran
S
Muniandy
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People; D060908:CTLA-4 Antigen / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006111:Graves Disease / Q000453:epidemiology / Q000235:genetics; D006239:Haplotypes; D050031:Hashimoto Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4