Genetic variants of Clock transcription factor are associated with individual susceptibility to obesity  

Oleh:

Sookoian, Silvia ; Gemma, Carolina ; Gianotti, Tomas Fernandez ; Burgueno, Adriana ; Castano, Gustavo

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The American Journal of Clinical Nutrition vol. 87 no. 06 (Jun. 2008), page 1606.
Topik: obesity and eating disorder

Ketersediaan

Perpustakaan FK Nomor Panggil: A07.K.2008.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Background:Altering circadian rhythmicity results in pathophysiologic changes resembling metabolic syndrome and fat accumulation. Objective:We investigated the role of gene variants and derived haplotypes of the CLOCK transcription factor in obesity and related quantitative metabolic traits. Design:Lean (n = 715) and overweight or obese (n = 391) unrelated subjects aged 34.4 ± 8.6 y were included in a population-based cross-sectional study. Six tag single-nucleotide polymorphisms (SNPs) with a minor (>10%) allele frequency (rs1554483 C/G; rs11932595 A/G; rs4580704 C/G; rs6843722 A/C; rs6850524 C/G, and rs4864548 A/G) encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > 0.8) were genotyped. Association was tested by PLINK and WHAP software, and multiple testing was controlled by permutation test. Results:The genotype frequencies of 4 tag SNPs—rs1554483, rs6843722, rs6850524, and rs4864548—had significant (empiric P < 0.010, 0.021, 0.021, and 0.010, respectively) associations with overweight or obesity. Haplotype analysis showed that only paired haplotypes, including rs1554483 and rs4864548, had a significant effect on overweight or obesity. Combinations of these SNPs (haplotype block CG and GA) are responsible for the gene effect (GA frequencies: 47% in cases, 41% in controls; empiric P < 0.011). These findings were concurrently observed in a sample of persons from a hospital-based study, and the combined Mantel-Haenszel fixed effect was an odds ratio of 1.82 (95% CI: 1.31, 2.54; P < 0.001) for the paired haplotype, which included CG and GA for rs1554483 and rs4864548. Conclusions:The present study suggests a putative role of the CLOCK polymorphism and related haplotypes in susceptibility to obesity. The haplotype of rs1554483G and rs4864548A was associated with a 1.8-fold risk of overweight or obesity.

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