Variants in the CNR1 and the FAAH genes and adiposity traits in the community.
Variants in the CNR1 and the FAAH genes and adiposity traits in the community.
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DOI：
10.1038/oby.2008.608
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发表时间：
2009-04
期刊：
影响因子：
6.9
通讯作者：
Fox, Caroline S.
中科院分区：
文献类型：
--
作者：
Lieb, Wolfgang;Manning, Alisa K.;Florez, Jose C.;Dupuis, Josee;Cupples, L. Adrienne;McAteer, Jarred B.;Vasan, Ramachandran S.;Hoffmann, Udo;O'Donnell, Christopher J.;Meigs, James B.;Fox, Caroline S.
内源性大麻素受体1的药物阻断导致体重减轻和改善超重和肥胖个体的代谢风险概况。我们假设CNR1（编码内源性大麻素受体1）和FAAH基因（编码脂肪酸酰胺水解酶，一种水解内源性大麻素的关键酶）的常见遗传变异与肥胖性状有关。我们在2415名Framingham后代研究参与者（平均年龄61±10岁；52.6%女性；平均BMI 28.2±5.4 kg/m2； 30.3%肥胖）中对CNR1基因的18个单核苷酸多态性（snp）和FAAH基因的9个snp进行了基因分型，并使用线性混合效应模型研究了它们与肥胖的横断面和纵向测量（体重指数[BMI]、腰围、BMI和腰围随时间的变化、内脏和皮下脂肪组织）的关联。所选择的snp捕获了CNR1位点85% （r2=0.8）的共同变异（次要等位基因频率bb0.5 %）和FAAH位点96% （r2=0.8）的共同变异（定义为包含上游+20 kb和下游+10 kb基因的基因组片段）。经多次检验校正，CNR1基因或FAAH基因的snp与BMI、腰围、内脏脂肪组织或皮下脂肪组织均无统计学相关性（P均为0.18）。尽管在大量未选择的样本中对基因及其调控区域进行了全面的SNP定位，但我们未能找到CNR1和FAAH基因常见变异与社区样本中肥胖测量相关的证据。
Pharmacologic blockade of the endocannabinoid receptor 1 leads to weight loss and an improved metabolic risk profile in overweight and obese individuals. We hypothesize that common genetic variants in the CNR1 (encoding endocannabinoid receptor 1) and FAAH genes (encoding fatty acid amide hydrolase, a key enzyme hydrolyzing endocannabinoids) are associated with adiposity traits. We genotyped 18 single nucleotide polymorphisms (SNPs) in the CNR1 and 9 SNPs in the FAAH gene in 2,415 Framingham Offspring Study participants (mean age 61±10 years; 52.6% women; mean BMI 28.2±5.4 kg/m2; 30.3% obese) and studied them for association with cross-sectional and longitudinal measures of adiposity (body mass index [BMI], waist circumference, change over time in BMI and waist circumference, visceral and subcutaneous adipose tissue) using linear mixed-effect models. The selected SNPs captured 85% (r2=0.8) of the common variation (minor allele frequency >5%) at the CNR1 locus and 96% (r2=0.8) of the common variation at the FAAH locus (defined as the genomic segment containing the gene +20 kb upstream and +10 kb downstream). After correction for multiple testing, none of the SNPs in the CNR1 gene or in the FAAH gene displayed statistical evidence for association with BMI, waist circumference and visceral adipose tissue or subcutaneous adipose tissue (all P>0.18). Despite comprehensive SNP mapping across the genes and their regulatory regions in a large unselected sample, we failed to find evidence for an association of common variants in the CNR1 and FAAH genes with measures of adiposity in our community-based sample.
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