ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity
ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity
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DOI：
10.2337/diabetes.55.02.06.db05-0971
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发表时间：
2006-02-01
期刊：
影响因子：
7.7
通讯作者：
Froguel, P
中科院分区：
文献类型：
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作者：
Bouatia-Naji, N;Meyre, D;Froguel, P
在一些人群中，脂联素编码基因ACDC中常见的单核苷酸多态性（snp）与胰岛素抵抗和2型糖尿病有关。在这里，我们研究了SNPs -11,377C >g, -11,391G>A, +45T >g和+276G >t在2,579名法国白种人（1,229名病态肥胖和1,350名对照）中的作用。我们发现严重形式的肥胖与-11,377C（优势比1.23,P = 0.001）和+276T（优势比1.19,P = 0.006）之间存在关联。令人惊讶的是，替代等位基因-11,377G和+276G先前已被报道为2型糖尿病的危险因素。传播不平衡试验显示，634例肥胖三人组中风险单倍型1((C))-1((G))-1((T))-2（(T)）有过传趋势（56.7%），包括-11,377C和+276T （P = 0.097）。来自普通人群的400个三胞胎的基于家庭的分析表明，肥胖单倍型与高脂联素水平之间存在关联，提示高脂联素血症在体重增加中的作用。然而，关于snp -11,377C>G和+276G>T对ACDC功能的推测作用的实验尚未得出结论。相比之下，在肥胖儿童（P = 0.005）和普通人群儿童（0.00007）中，启动子SN-P -11,391G>A与较高的脂联素水平相关。体外转录分析表明-11,391A可能增加ACDC活性。总之，我们的研究表明，ACDC/脂联素基因的变异与严重肥胖的风险有关。然而，这些可能的联系背后的机制还不完全清楚。
Common single nucleotide polymorphisms (SNPs) in the ACDC adiponectin encoding gene have been associated with insulin resistance and type 2 diabetes in several populations. Here, we investigate the role of SNPs -11,377C>G, -11,391G>A, +45T>G, and +276G>T in 2,579 French Caucasians (1,229 morbidly obese and 1,350 control subjects). We found an association between severe forms of obesity and -11,377C (odds ratio 1.23, P = 0.001) and +276T (1.19, P = 0.006). Surprisingly, alternative alleles -11,377G and +276G have been previously reported as risk factors for type 2 diabetes. Transmission disequilibrium tests showed a trend in overtransmission (56.7%) of a risk haplotype 1((C))-1((G))-1((T))-2((T)) including -11,377C and +276T in 634 obesity trios (P = 0.097). Family-based analysis in 400 trios from the general population indicated association between obesity haplotype and higher adiponectin levels, suggesting a role of hyperadiponectinemia in weight gain. However, experiments studying the putative roles of SNPs -11,377C>G and +276G>T on ACDC functionality were not conclusive. In contrast, promoter SN-P -11,391G>A was associated with higher adiponectin levels in obese children (P = 0.005) and in children from the general population (0.00007). In vitro transcriptional assays showed that -11,391A may increase ACDC activity. In summary, our study suggests that variations at the ACDC/adiponectin gene are associated with risk of severe forms of obesity. However, the mechanisms underlying these possible associations are not fully understood.