Adaptive human CDKAL1 variants underlie hormonal response variations at the enteroinsular axis

Recent analyses have identified positively selected loci that explain differences in immune responses, body forms, and adaptations to extreme climates, but variants that describe adaptations in energy-balance regulation remain underexplored. To identify variants that confer adaptations in energy-bal...

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Bibliographic Details
Published in:PloS one 2014-09, Vol.9 (9), p.e105410-e105410
Main Authors: Chang, Chia Lin, Cai, James J, Huang, Shang Yu, Cheng, Po Jen, Chueh, Ho Yen, Hsu, Sheau Yu Teddy
Format: Article
Language:English
Subjects:
Adaptation
Adaptations
Asian Continental Ancestry Group - genetics
Biological evolution
Biology and Life Sciences
Body mass index
Climate
Climatic extremes
Cyclin-Dependent Kinase 5 - genetics
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - genetics
Energy balance
Energy Metabolism - genetics
Evolution, Molecular
Female
Gastric Inhibitory Polypeptide - genetics
Gene expression
Gene Frequency
Genes
Genetic Association Studies
Genetic Predisposition to Disease
Genomes
Genotype
Glucose
Glucose tolerance
Glucose Tolerance Test
Gynecology
Haplotypes
Health risks
Hospitals
Human populations
Humans
Immune response
Immunological tolerance
Insulin
Linkage Disequilibrium
Medicine and Health Sciences
Metabolism
Obesity
Obstetrics
Peroxisome proliferator-activated receptors
Physiology
Polymorphism, Single Nucleotide
Polypeptides
Population genetics
PPAR gamma - genetics
Pregnancy
Regulation
Selection, Genetic
Serum levels
Simulation analysis
Single-nucleotide polymorphism
Statistical analysis
Studies
tRNA Methyltransferases
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Summary:Recent analyses have identified positively selected loci that explain differences in immune responses, body forms, and adaptations to extreme climates, but variants that describe adaptations in energy-balance regulation remain underexplored. To identify variants that confer adaptations in energy-balance regulation, we explored the evolutionary history and functional associations of candidate variants in 207 genes. We screened single nucleotide polymorphisms in genes that had been associated with energy-balance regulation for unusual genetic patterns in human populations, followed by studying associations among selected variants and serum levels of GIP, insulin, and C-peptide in pregnant women after an oral glucose tolerance test. Our analysis indicated that 5' variants in CDKAL1, CYB5R4, GAD2, and PPARG are marked with statistically significant signals of gene-environment interactions. Importantly, studies of serum hormone levels showed that variants in CDKAL1 are associated with glucose-induced GIP and insulin responses (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0105410