Center for Genome Information, Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Cincinnati, OH 45267, USA.
BMC Med Genet. 2009 Dec 22;10:143. doi: 10.1186/1471-2350-10-143.
A genome wide association study found significant association of a sequence variant, rs7566605, in the insulin-induced gene 2 (INSIG2) with obesity. However, the association remained inconclusive in follow-up studies. We tested for association of four tagging SNPs (tagSNPs) including this variant with body mass index (BMI) and abdominal circumference (ABDCIR) in the Samoans of the Western Pacific, a population with high levels of obesity.
We studied 907 adult Samoan participants from a longitudinal study of adiposity and cardiovascular disease risk in two polities, American Samoa and Samoa. Four tagSNPs were identified from the Chinese HapMap database based on pairwise r2 of >or=0.8 and minor allele frequency of >or=0.05. Genotyping was performed using the TaqMan assay. Tests of association with BMI and ABDCIR were performed under the additive model.
We did not find association of rs7566605 with either BMI or ABDCIR in any group of the Samoans. However, the most distally located tagSNPs in Intron 3 of the gene, rs9308762, showed significant association with both BMI (p-value 0.024) and ABDCIR (p-value 0.009) in the combined sample and with BMI (p-value 0.038) in the sample from Samoa.
Although rs7566605 was not significantly associated with obesity in our study population, we can not rule out the involvement of INSIG2 in obesity related traits as we found significant association of another tagSNP in INSIG2 with both BMI and ABDCIR. This study suggests the importance of comprehensive assessment of sequence variants within a gene in association studies.
全基因组关联研究发现，胰岛素诱导基因 2（INSIG2）中的一个序列变异 rs7566605 与肥胖显著相关。然而，后续研究的结果并不一致。我们在太平洋西部肥胖人群萨摩亚人中，测试了包括该变异在内的四个标记单核苷酸多态性（tagSNPs）与体重指数（BMI）和腹围（ABDCIR）的相关性。
我们研究了来自两个政治体（美属萨摩亚和萨摩亚）的肥胖和心血管疾病风险纵向研究中的 907 名成年萨摩亚参与者。根据中国 HanMap 数据库中 r2>or=0.8 和次要等位基因频率>or=0.05 的双等位基因，从该数据库中确定了四个 tagSNPs。使用 TaqMan 分析方法进行基因分型。采用加性模型进行与 BMI 和 ABDCIR 的关联检验。
我们没有发现 rs7566605 与萨摩亚人任何一组的 BMI 或 ABDCIR 相关。然而，基因内 3 号内含子中最远端的 tagSNP rs9308762 与 BMI（p 值 0.024）和 ABDCIR（p 值 0.009）在合并样本中，与 BMI（p 值 0.038）在萨摩亚样本中均呈显著相关。
尽管 rs7566605 在我们的研究人群中与肥胖无显著相关性，但我们不能排除 INSIG2 参与肥胖相关特征，因为我们发现 INSIG2 中的另一个 tagSNP 与 BMI 和 ABDCIR 均显著相关。本研究提示在关联研究中，全面评估基因内序列变异的重要性。
