Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

Abstract

Background: Transcription factor 7-like 2 gene (TCF7L2), fat mass and obesity-associated gene (FTO), and ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) are known risk loci for type 2 diabetes (T2DM) mostly in European populations. Objectives: To assess the association of these genes with T2DM risk in a South African mixed-ancestry population. Methods: Five hundred and sixty six participants were genotyped for ENPP1-rs997509 and -rs1044498, FTO-9941349 and -rs3751812, TCF7L2-rs12255372 and -rs7903146 polymorphisms using Taqman genotyping assays and validated by automated sequencing to assess the association of the polymorphisms with cardiometabolic traits. Results: In logistic regression models adjusted for age, sex, body mass index (BMI) and insulin resistance, minor allele of rs997509 was associated with a higher risk of prevalent T2DM under a recessive model [odd ratio 4.60 (95% confidence interval: 1.07 to 19.86); p = 0.040].Under additive model, the rs7903146 [1.43 (1.00 to 2.04); p= 0.053] and rs9941349 [1.43 (1.00 to 2.04); p = 0.052] minor alleles showed marginally significant associations with a high risk of T2DM. However, only the rs7903146 alleles (p=0.011) and genotypes (p=0.025) distributions were statistically significantly different between diabetic and non-diabetic individuals. Conclusion: Our findings demonstrate that ENPP1, TCF7L2, and FTO may predispose to T2DM in the mixed-ancestry population.

Glucose Tolerance,MTHFRC677T andNOS3G894T Polymorphisms, and Global DNA Methylation in Mixed Ancestry African Individuals

“…All participants who were recruited for the study voluntarily signed written consent after the procedures had been fully explained in the language of their choice. Permission to conduct the study was granted by relevant authorities such as city and community authorities as previously described [20]. …”

“…Clinical data which has been previously described [20] was collected in the form of a standardized questionnaire. During this time physical examination was conducted with data collection on blood pressure according to World Health Organization (WHO) guidelines [23] using a semiautomatic digital blood pressure monitor (Rossmax PA, USA) on the right arm in sitting position and anthropometric measurements.…”

“…Blood samples were collected from participants after overnight fast and processed as described in [20]. Plasma glucose levels and glycated haemoglobin (HbA1c) in whole blood collected in an EDTA tube were measured, respectively, by enzymatic hexokinase method and the turbidimetric inhibition immunoassay (Cobas 6000, Roche Diagnostics, Germany).…”

TCF7L2 rs290481 T>C polymorphism is associated with an increased risk of type 2 diabetes mellitus and fasting plasma glucose level

“…Among these single nucleotide polymorphisms (SNPs), the TCF7L2 rs7903146 polymorphism are widely studied for the potential relationship with T2DM susceptibility. Recently, several case-control studies found that TCF7L2 rs7903146 C>T is associated with the development of T2DM [ 9 – 12 ]. Then, a meta-analysis suggested that TCF7L2 rs7903146 C>T variants might confer an increased risk to T2DM in Chinese Han population [ 13 ].…”

The association of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) K121Q gene polymorphism with the risk of type 2 diabetes mellitus in European, American, and African populations: a meta-analysis

“…A study found that the 121Q variant had a greater inhibitory action on IR compared to the 121K variant (13 (20) showed that the ENPP1 K121Q gene polymorphism was associated with increased risk of T2DM. Whereas several other studies (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) showed that the ENPP1 K121Q gene polymorphism had no significant association with increased risk of T2DM. A meta-analysis study is required to determine the actual association of the above-mentioned studies.…”