A polymorphism in the 5′ untranslated region of the human ob gene is associated with low leptin levels
A polymorphism in the 5′ untranslated region of the human ob gene is associated with low leptin levels
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DOI：
10.1038/sj.ijo.0800567
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发表时间：
1998-03-01
影响因子：
4.9
通讯作者：
Froguel, P
中科院分区：
文献类型：
--
作者：
Hager, J;Clement, K;Froguel, P
目的：目的：寻找人肥胖基因ob突变并评价其在肥胖症发病中的作用，设计：基因突变直接筛查及病例对照研究，多因素分析评价临床指标的差异。关联研究：395例不相关的病态肥胖受试者结果：我们发现了人ob基因外显子1的一个DNA变异（A - >G置换，碱基+19），该变异在我们的研究人群中的患病率为62%。不同遗传模型下的关联分析（显性，共显性，隐性）没有显示出该变异与BMI相关的显著证据，然而，在校正BMI后，与A等位基因杂合子或纯合子的肥胖患者相比，G等位基因纯合子的肥胖个体显示出显著较低的瘦素浓度。最近的连锁研究表明hsob基因座与肥胖有连锁关系。我们的研究提供了进一步的证据表明，与外显子1的G-等位基因连锁不平衡的ob基因的缺陷可能通过影响瘦素浓度参与肥胖。
OBJECTIVE: To search the human ob gene for mutations and evaluate their role in massive obesity.DESIGN: Direct mutation screening of the gene and case-control association study, Multivariate analyses for evaluation of differences in clinical parameters.SUBJECTS: Primary mutation screening: 24 morbidly obese subjects (body mass index (BMI) > 40 kg/m(2)). Association study: 395 unrelated morbidly obese subjects (BMI > 40 kg/m(2)), 121 lean, non-diabetic control individuals, 72 women of a random sample with an average BMI 32.5 kg/m(2).RESULTS: We report the finding of a DNA variant in exon 1 of the human ob gene (A - >G substitution, base + 19), This variant showed a prevalence of 62% in our study population. Association analyses under different genetic models (dominant, co-dominant, recessive) showed no significant evidence for an association of this variant with BMI, However, obese individuals homozygous for the G-allele showed significantly lower leptin concentrations compared to obese patients either heterozygous or homozygous for the A-allele after correction for BMI.CONCLUSION: Recent linkage studies have shown evidence for linkage of the hsob locus with obesity. Our study provides further evidence that a defect in the ob gene in linkage disequilibrium with the G-allele of exon 1 might be involved in obesity by affecting leptin concentrations.