Genetic Associations of PPARGC1A with Type 2 Diabetes: Differences among Populations with African Origins.

Amanpreet K Cheema,Gustavo G Zarini,Mehmet T Dorak,Juan P Liuzzi,Tan Li,Fatma G Huffman

doi:10.1155/2015/921274

Amanpreet K Cheema, Gustavo G Zarini + Show 4 more

Open Access

https://doi.org/10.1155/2015/921274

Copy DOI

Abstract

The aim of this study was to assess the differences in correlation of PPARGC1A polymorphisms with type 2 diabetes (T2D) risk in adults of African origins: African Americans and Haitian Americans. The case-control study consisted of >30 years old, self-identified Haitian Americans (n = 110 cases and n = 116 controls) and African Americans (n = 124 cases and n = 122 controls) living in South Florida with and without T2D. Adjusted logistic regression indicated that both SNP rs7656250 (OR = 0.22, P = 0.005) and rs4235308 (OR = 0.42, P = 0.026) showed protective association with T2D in Haitian Americans. In African Americans, however, rs4235308 showed significant risk association with T2D (OR = 2.53, P = 0.028). After stratification with sex, in Haitian Americans, both rs4235308 (OR = 0.38, P = 0.026) and rs7656250 (OR = 0.23, P = 0.006) showed protective association with T2D in females whereas in African American males rs7656250 had statistically significant protective effect on T2D (OR = 0.37, P = 0.043). The trends observed for genetic association of PPARGC1A SNPs, rs4235308, and rs7656250 for T2D between Haitian Americans and African Americans point out differences in Black race and warrant replicative study with larger sample size.

Highlights

Peroxisome proliferator activated receptor, gamma, coactivator 1 alpha (PPARGC1A) gene encodes a well-known protein, PGC-1α [1,2,3,4,5]
Ethnic heterogeneity observed in genetic associations of PPARGC1A polymorphisms with type 2 diabetes (T2D) could be due to the presence of causal or other polymorphisms in strong linkage disequilibrium (LD) with the polymorphism in question [11,12,13,14]
Body mass index (BMI) was significantly higher for cases as compared to controls in African Americans only (P < 0.001)

Summary

Introduction

Peroxisome proliferator activated receptor, gamma, coactivator 1 alpha (PPARGC1A) gene encodes a well-known protein, PGC-1α [1,2,3,4,5]. Upregulation of glucose transporter-4 (GLUT-4) by PGC-1α increases glucose uptake in skeletal muscle cells and increases phosphoenolpyruvate carboxy-kinase and glucose-6-phosphatase activities [7, 8]. This versatility of PGC-1α as a master coactivator of various metabolic processes has put it on a center stage for variety of human metabolic diseases such as type 2 diabetes (T2D) [9]. The environment in which populations live varies around the world This variation in the interaction of environment with gene of interest could be instrumental in different associations of PPARGC1A polymorphisms with T2D across ethnicities

Objectives

Methods

Results

Discussion

Conclusion