Meyre David, Farge Morgane, Lecoeur Cécile, Proenca Christine, Durand Emmanuelle, Allegaert Frédéric, Tichet Jean, Marre Michel, Balkau Beverley, Weill Jacques, Delplanque Jérôme, Froguel Philippe
CNRS 8090-Institute of Biology, Pasteur Institute, Lille, France.
Hum Mol Genet. 2008 Jun 15;17(12):1798-802. doi: 10.1093/hmg/ddn070. Epub 2008 Mar 5.
Stone et al. previously reported an association between the TBC1D1 gene variant R125W (rs35859249) and severe obesity in women from US pedigrees. We attempted to replicate this result in 9714 French Caucasian individuals, combining family-based and general population studies. We confirmed an association with familial obesity (defined as body mass index (BMI) > or = 97th percentile) in women from 1109 obesity-selected pedigrees (Z-score = 2.70, P = 0.008). Analysis of 16 microsatellite markers on chromosome 4 restricted to the 42 pedigrees carrying the TBC1D1 R125W variant allele also revealed a suggestive evidence of linkage with obesity (maximum likelihood binomial LOD of 2.73, P = 0.0002) on chromosome 4p14, where resides TBC1D1. In contrast, R125W variant was neither associated with BMI nor with obesity in a large population-based cohort. These results confirm a putative role of TBC1D1 R125W variant in familial obesity predisposition.
斯通等人此前报道，TBC1D1基因变体R125W（rs35859249）与来自美国谱系的女性严重肥胖之间存在关联。我们试图在9714名法国白种人中重复这一结果，结合基于家庭和一般人群的研究。我们证实，在1109个肥胖选择谱系的女性中，该变体与家族性肥胖（定义为体重指数（BMI）≥第97百分位数）有关联（Z分数=2.70，P=0.008）。对4号染色体上16个微卫星标记的分析仅限于携带TBC1D1 R125W变异等位基因的42个谱系，这也揭示了在TBC1D1所在的4号染色体p14上与肥胖存在连锁的提示性证据（最大似然二项式LOD为2.73，P=0.0002）。相比之下，在一个大型基于人群的队列中，R125W变体与BMI或肥胖均无关联。这些结果证实了TBC1D1 R125W变体在家族性肥胖易感性中的假定作用。
