Common Polymorphisms Linked to Obesity and Cardiovascular Disease in Europeans and Asians are Associated with Type 2 Diabetes in Mexican Mestizos.

Angélica Saraí Jiménez-Osorio,Oscar Medina-Contreras,Jacqueline Solares-Tlapechco,Julio Granados,Martha Eunice Rodríguez-Arellano,Paula Costa-Urrutia,Helios Cárdenas-Hernández,Catalina López-Saucedo,Claudette Musalem-Younes,Teresa Estrada-Garcia

doi:10.3390/medicina55020040

Abstract

Background and objectives: Type 2 diabetes (T2D) is a major problem of public health in Mexico. We investigated the influence of five polymorphisms, previously associated with obesity and cardiovascular disease in Europeans and Asians, on T2D in Mexican Mestizos. Materials and Methods: A total of 1358 subjects from 30 to 85 years old were genotyped for five loci: CXCL12 rs501120; CDNK2A/B rs1333049; HNF-1α rs2259816; FTO rs9939609; and LEP rs7799039. We used logistic regressions to test the effect of each locus on T2D in two case–control groups with obesity and without obesity. Also, linear regression models on glucose and glycated hemoglobin (HbA1c) were carried out on the whole sample, adjusted by age, gender, and body mass index. Results: The CXCL12 rs501120 C allele (OR = 1.96, p = 0.02), the FTO rs9939609 A allele (OR = 2.20, p = 0.04) and the LEP rs7799039 A allele (OR = 0.6, p = 0.03) were significantly associated with T2D in obesity case–control group. No significant association was found in the non-obesity case–control group. The linear regression model showed that CDNK2A/B rs1333049 C allele (β = 0.4, p = 0.03) and FTO rs9939609 A allele (β = 0.5, p = 0.03), were significantly associated with HbA1c, but no association was found among the loci with the glucose levels. Conclusions: Polymorphisms previously linked with obesity and cardiovascular events were also associated with T2D and high levels of HbA1c. Furthermore, we must point at the fact that this is the first report where polymorphisms CXCL12 rs501120 and LEP rs7799039 are associated with T2D in subjects with obesity.

Highlights

Obesity contributes to the development of hyperinsulinemia, hyperglycemia, dyslipidemia, oxidative stress, and inflammation
To contribute to a better understanding of the basis of type 2 diabetes (T2D) genomics in Mexico, we evaluated if the selected common polymorphisms, previously linked to obesity and cardiovascular disease in European and Asian populations, are associated with T2D in a Mexican Mestizo population
Our results showed that CXCL12 rs501120, LEP rs7799039, and FTO rs9939609 polymorphisms were associated with T2D in subjects with obesity, but not in subjects without obesity

Summary

Introduction

Obesity contributes to the development of hyperinsulinemia, hyperglycemia, dyslipidemia, oxidative stress, and inflammation. It is well known that subjects with obesity have an increased risk to develop type 2 diabetes (T2D) and cardiovascular events [1]. Medicina 2019, 55, 40 of environmental and genetic factors; some families present higher incidence of that disease than others, as well as diverse Mexican Native-American groups [2]. Obesity is the main health problem in Mexico as it has the highest prevalence, worldwide, in children obesity and the second in adult obesity. Mexico ranks fifth in T2D prevalence [5] and the search for genetic factors has taken an important place in T2D research. Type 2 diabetes (T2D) is a major problem of public health in Mexico. We investigated the influence of five polymorphisms, previously associated with obesity and cardiovascular disease in Europeans and Asians, on T2D in Mexican Mestizos.

Methods

Discussion

Conclusion