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

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.

SUBMITTER: Cheema AK

PROVIDER: S-EPMC4419207 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Cheema Amanpreet K AK Li Tan T Liuzzi Juan P JP Zarini Gustavo G GG Dorak Mehmet T MT Huffman Fatma G FG

Journal of diabetes research 20150421

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 ...[more]

PMID: 25977930

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Project description:Type 2 diabetes (T2D) is a complex disease characterized by beta cell dysfunctions. Islet amyloid polypeptide (IAPP) is highly conserved and co-secreted with insulin with over 40% of autopsy cases of T2D showing islet amyloid formation due to IAPP aggregation. Dysregulation in IAPP processing, stabilization and degradation can cause excessive oligomerization with beta cell toxicity. Previous studies examining genetic associations of pathways implicated in IAPP metabolism have yielded conflicting results due to small sample size, insufficient interrogation of gene structure and gene-gene interactions. In this multi-staged study, we screened 89 tag single nucleotide polymorphisms (SNPs) in 6 candidate genes implicated in IAPP metabolism and tested for independent and joint associations with T2D and beta cell dysfunctions. Positive signals in the stage-1 were confirmed by de novo and in silico analysis in a multi-centre unrelated case-control cohort. We examined the association of significant SNPs with quantitative traits in a subset of controls and performed bioinformatics and relevant functional analyses. Amongst the tag SNPs, rs1583645 in carboxypeptidase E (CPE) and rs6583813 in insulin degrading enzyme (IDE) were associated with 1.09 to 1.28 fold increased risk of T2D (P Meta?=?9.4×10(-3) and 0.02 respectively) in a meta-analysis of East Asians. Using genetic risk scores (GRS) with each risk variant scoring 1, subjects with GRS?3 (8.2% of the cohort) had 56% higher risk of T2D than those with GRS?=?0 (P?=?0.01). In a subcohort of control subjects, plasma IAPP increased and beta cell function index declined with GRS (P?=?0.008 and 0.03 respectively). Bioinformatics and functional analyses of CPE rs1583645 predicted regulatory elements for chromatin modification and transcription factors, suggesting differential DNA-protein interactions and gene expression. Taken together, these results support the importance of dysregulation of IAPP metabolism in T2D in East Asians.

Dataset Information

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

Publications

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

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