Association between angiopoietin-like 6 (ANGPTL6) gene polymorphisms and metabolic syndrome-related phenotypes in the French MONICA Study
Association between angiopoietin-like 6 (ANGPTL6) gene polymorphisms and metabolic syndrome-related phenotypes in the French MONICA Study
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DOI：
10.1016/j.diabet.2008.12.005
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发表时间：
2009-09-01
影响因子：
7.2
通讯作者：
Meirhaeghe, A.
中科院分区：
文献类型：
--
作者：
Legry, V.;Goumidi, L.;Meirhaeghe, A.
目的。 - 虽然目前已知ANGPTL6（血管生成素样6）基因产物参与小鼠脂肪量和胰岛素敏感性的调节，但其在人类中的生理功能尚未确定。 - 对来自基于人群的法国 MONICA 研究 (n = 3402) 的受试者进行 ANGPTL6 中单核苷酸多态性 (SNP) 的基因分型，并寻找与人体测量或生化表型的关联。结果。 - 在连锁不平衡作图基础上评估 100 名随机选择的受试者中 17 个 ANGPTL6 SNP 的频率时，发现 4 个 SNP（rs6511435、rs8112063、rs1671983 和 rs15723）覆盖了 95% 以上的已知 ANGPTL6 遗传变异性。然后对整个 MONICA 研究的受试者进行这四个 SNP 的基因分型。未检测到 rs11671983 和 rs15723 的显着关联。相反，rs8112063 的 G 等位基因与较低的血浆葡萄糖水平相关（P = 0.009）。此外，携带 rs6511435 G 等位基因的肥胖受试者的血浆胰岛素水平高于 AA 受试者（P=0.0055）。此外，rs6511435 的 G 等位基因往往与升高 20% 的代谢综合征风险相关（P=0.034）。然而，当应用错误发现率测试（40 次测试）时，这些关联不再具有统计显着性。结论。 - 这些发现构成了第一项针对人类 ANGPTL6 遗传变异性的研究。尽管没有证据表明 ANGPTL6 的多态性可能与代谢综合征相关表型显着相关，但不能排除这些多态性与这些参数的弱关联。需要进一步的关联研究才能得出任何明确的结论。 (C) 2009 Elsevier Masson SAS。版权所有。
Aim. - Although the ANGPTL6 (angiopoietin-like 6) gene product is now known to be involved in the regulation of fat mass and insulin sensitivity in mice, its physiological functions in humans have yet to be determined.Methods. - Subjects from the population-based French MONICA Study (n = 3402) were genotyped for Single nucleotide polymorphisms (SNPs) in ANGPTL6, and associations with anthropometric or biochemical phenotypes were looked for.Results. - On evaluating the frequency of 17 ANGPTL6 SNPs in 100 randomly selected subjects oil the basis of linkage disequilibrium mapping, four SNPs (rs6511435, rs8112063, rs1671983 and rs15723) were found to cover more than 95% of the known ANGPTL6 genetic variability. Subjects from the entire MONICA Study were then genotyped for these four SNPs. No significant association was detected for rs11671983 and rs15723. In contrast, the G allele of rs8112063 was associated with lower plasma glucose levels (P = 0.009). Also, obese subjects carrying the G allele of rs6511435 had higher plasma insulin levels than AA subjects (P=0.0055). Moreover, the G allele of rs6511435 tended to be associated with a 20% higher risk of the metabolic syndrome (P=0.034). However, when false discovery rate testing (40 tests.) was applied, these associations were no longer statistically significant.Conclusion. - These findings constitute the first study in humans of ANGPTL6 genetic variability. Although there was no evidence that polymorphisms in ANGPTL6 might be significantly associated with the metabolic syndrome-related phenotypes, a weak association of these polymorphisms with these parameters cannot be excluded. Further association Studies are needed to arrive at any definite conclusions. (C) 2009 Elsevier Masson SAS. All rights reserved.