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

Abstract

BackgroundGenetic 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).MethodTen 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.ResultsDominant, 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.ConclusionsDPP4 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.

Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus

“…Mature DPP4 is embedded in the plasma membrane as a homodimer and each monomer consists of an N-terminal cytoplasmic domain, followed by a transmembrane domain and a large ectodomain, which can be further subdivided into a short stalk domain, a glycosylation-rich and a cysteine-rich region as well as the C-terminal catalytic domain (α/ β-hydrolase domain) [26]. Polymorphisms in the DPP4 gene were implicated in several diseases and conditions, including diabetes [27,28] and myocardial infarction [29] but their potential impact on MERS-CoV infection has not been analyzed.…”

Hypertension and Type 2 Diabetes Are Associated With Decreased Inhibition of Dipeptidyl Peptidase-4 by Sitagliptin

“…We found that the rs4664446 GG genotype (homozygous wild type) was associated with lower DPP4 antigen levels during placebo. Ahmed et al reported that a different SNP variant, rs4664443 G>A, is associated with both diabetes and increased circulating DPP4 antigen concentrations in Malaysian individuals with T2DM [ 27 ]. They did not report testing for variants of rs4664446.…”

DPP4 Polymorphisms Are Associated With Hypoalphalipoproteine mia and DPP4 Serum Levels. A Case-control Study of the GEA Cohort.

“…Moreover, DPP4 is an adipokine with increased expression in obesity [10,16], FL [17], and type 2 diabetes mellitus (T2DM) [18] abnormalities that coexist with chronic in ammation. Several single nucleotide polymorphisms (SNPs) have been described in the DPP4 gene (located in region 2q24.3), some of which have been associated with rheumatoid arthritis [19], T2DM, variation in DPP4 [20] and apolipoprotein B (apo B) levels [21], and with increased risk of myocardial infarction in patients with coronary artery disease (CAD) [22]. Considering the high prevalence of obesity and comorbidities such as T2DM [23] and HA in the Mexican population [3] and that the expression of DPP4 is increased in these abnormalities, the aim of the present study was to evaluate the association of the DPP4 polymorphisms with the presence of HA and with DPP4 levels in a cohort of Mexican individuals.…”