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极度肥胖儿童及青少年中细胞因子信号转导抑制因子(SOCS)-3基因序列变异分析

Analysis of sequence variations in the suppressor of cytokine signaling (SOCS)-3 gene in extremely obese children and adolescents.

作者信息

Hölter Katja, Wermter Anne-Kathrin, Scherag André, Siegfried Wolfgang, Goldschmidt Hanspeter, Hebebrand Johannes, Hinney Anke

机构信息

Clinical Research Group, Department of Child and Adolescent Psychiatry, Philipps-University of Marburg, Germany.

出版信息

BMC Med Genet. 2007 Apr 19;8:21. doi: 10.1186/1471-2350-8-21.

Abstract

BACKGROUND

The suppressor of cytokine signaling (SOCS)-3 is a negative feedback regulator of cytokine signaling and also influences leptin signaling. We investigated association of variations in the coding sequence and promoter region of SOCS3 with extreme obesity in German children and adolescents.

METHODS

An initial screen for sequence variations in 181 extremely obese children and adolescents and 188 healthy underweight adults revealed two previously reported single nucleotide polymorphisms (SNPs) in the SOCS3 5' region: -1044 C>A (numbering refers to bases upstream of ATG in exon 2) within a predicted STAT3 binding element and -920 C>A (rs12953258, for numbering, see above).

RESULTS

We did not detect significant differences in allele or genotype frequencies for any of these SNPs between the analysed study groups (all nominal p > 0.2). In addition, we performed a pedigree transmission disequilibrium test (PDT) for the SNP -1044 C>A in families comprising 703 obese children and adolescents, 281 of their obese siblings and both biological parents. The PDT revealed no transmission disequilibrium (nominal p > 0.05).

CONCLUSION

In conclusion, our data do not suggest evidence for a major role of the respective SNPs in SOCS3 in the pathogenesis of extreme obesity in our study groups.

摘要

背景

细胞因子信号转导抑制因子(SOCS)-3是细胞因子信号转导的负反馈调节因子,也影响瘦素信号转导。我们研究了德国儿童和青少年中SOCS3编码序列和启动子区域变异与极端肥胖的相关性。

方法

对181名极端肥胖儿童和青少年以及188名健康体重过轻成年人的序列变异进行初步筛查,发现在SOCS3 5'区域有两个先前报道的单核苷酸多态性(SNP):预测的STAT3结合元件内的-1044 C>A(编号指外显子2中ATG上游的碱基)和-920 C>A(rs12953258,编号见上文)。

结果

我们在分析的研究组之间未检测到这些SNP中任何一个的等位基因或基因型频率有显著差异(所有名义p>0.2)。此外,我们对包含703名肥胖儿童和青少年、281名肥胖同胞及其亲生父母的家庭中的SNP -1044 C>A进行了家系传递不平衡检验(PDT)。PDT未显示传递不平衡(名义p>0.05)。

结论

总之,我们的数据不支持在我们的研究组中,SOCS3中相应SNP在极端肥胖发病机制中起主要作用的证据。

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