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Allelic imbalance in glucose‐dependent insulinotropic polypeptide (GIP) gene expression
Author(s) -
Hsu Sheauyu Teddy,
Chang Chia Lin
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1070.6
Subject(s) - biology , incretin , gene , single nucleotide polymorphism , gastric inhibitory polypeptide , genetics , population , receptor , phenotype , hormone , endocrinology , type 2 diabetes , diabetes mellitus , glucagon , medicine , environmental health , genotype
Recent genomic analyses have revealed a number of SNPs that are associated with human adaptations in immune responses, body forms, or adaptations to extreme climates in select human populations. To systematically analyze the contributions of genetic variations in polypeptide hormones and their cognate receptors to physiological diversities in humans, we have recently studied SNPs in 839 ligand and receptor genes and identified the glucose‐dependent insulinotropic polypeptide (GIP) as a positively selected gene in Eurasians, suggesting that GIP polymorphisms could contribute to phenotypic variations in carbohydrate and lipid metabolism among humans. To gain a better understanding of the underlying mechanism of the selection, we analyzed GIP promoter reporters in vitro and the expression of GIP transcripts in human tissues. Because both assays showed that GIP expression is haplotype‐dependent, we concluded that three regulatory variants in the GIP promoter could represent causal mutations that contributed to the population genetics observation. Taken together, our study has highlighted an unexpected complexity in the regulation of an incretin hormone that is crucial to normal energy‐balance regulation; it has also illuminated the importance of understanding adaptations in genes associated with energy‐balance regulation in the face of the emerging pandemics of diabetes and obesity in modern society.