Gender-specific associations between ADIPOQ gene polymorphisms and adiponectin levels and obesity in the Jackson Heart Study cohort.
Gender-specific associations between ADIPOQ gene polymorphisms and adiponectin levels and obesity in the Jackson Heart Study cohort.
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DOI：
10.1186/s12881-015-0214-x
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发表时间：
2015-08-20
影响因子：
--
通讯作者：
Davis SK
中科院分区：
文献类型：
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作者：
Riestra P;Gebreab SY;Xu R;Khan RJ;Bidulescu A;Correa A;Tekola-Ayele F;Davis SK
尽管脂联素在调节一般代谢稳态中发挥着重要作用，但对非裔美国人人群脂联素遗传决定因素和相关心脏代谢特征的分析仍然有限且不一致。考虑到非裔美国人的高遗传混合性以及可能混淆遗传性状关联的重要人口分层，这项工作的目的是对来自杰克逊心脏研究 (JHS) 队列的大量非裔美国人中 ADIPOQ 变异与脂联素水平和肥胖表型之间的关联进行全面分析。 2968 名 JHS 参与者（1131 名男性；1837 名女性）的基因型数据可用。通过标签-SNP 方法和文献综述选择单核苷酸多态性 (SNP)。使用 IMPUTE2 软件和来自 1000G 项目的参考阶段数据进行基因型插补。 PLINK软件用于遗传分析。通过 ELISA 分析血浆样本的脂联素水平。所有分析均通过使用血统信息标记 (AIM) 在 HAPMIX 中计算的欧洲血统个体比例 (PEA) 估计值进行人口分层控制。我们发现一些 ADIPOQ 变体与脂联素水平存在性别依赖性关联。在女性中，经 Bonferroni 校正并控制 PEA 百分比、年龄、家庭年收入和吸烟后，所研究的四个多态性（rs6444174、rs16861205、rs1403697、rs7641507）与脂联素水平相关。这些结果与单倍型分析一致。 rs12495941 变异与肥胖之间的关联受到 PEA 的调节，因此 G 等位基因与肥胖发生率较高之间的关系存在于低 PEA 组的个体中。此外，我们发现肥胖对 ADIPOQ rs6444174 SNP 和 BMI 之间的关联有影响，因此 T 等位基因的存在仅在体重正常的参与者中与 BMI 呈显着负相关。在这个大型非裔美国人队列中，ADIPOQ 变体以性别依赖性方式与脂联素水平相关，其中一些变体与肥胖和 BMI 的关系分别受到 PEA 和肥胖状态的调节。这表明这些多态性对脂联素和肥胖表型的影响受到非裔美国人群体遗传和环境因素的强烈相互作用。本文的在线版本 (doi:10.1186/s12881-015-0214-x) 包含补充材料，可供授权用户使用。
Despite the important role of adiponectin in regulating general metabolic homeostasis, analysis of genetic determinants of adiponectin and the related cardio-metabolic traits in African American population has been limited and inconsistent. Considering the high genetic admixture of African Americans and thus the important population stratification that may confound the genetic-trait associations, the objective of this work was to perform a comprehensive analysis of the associations between ADIPOQ variants and adiponectin levels and obesity phenotypes in a large African American population from the Jackson Heart Study (JHS) cohort. Genotype data was available for 2968 JHS participants (1131men; 1837women). Single Nucleotide Polymorphisms (SNPs) were selected by a Tag-SNP Approach and literature review. The genotype imputation was performed using IMPUTE2 software and reference phased data from the 1000G project. PLINK software was used for the genetic analysis. Plasma specimens were analyzed by ELISA for adiponectin levels. All analyses were controlled for population stratification assessed by Individual Proportions of European Ancestry (PEA) estimates calculated in HAPMIX using ancestry informative markers (AIMs). We found a gender-dependent association of some ADIPOQ variants and adiponectin levels. In women four of the studied polymorphisms (rs6444174, rs16861205, rs1403697, rs7641507) were associated with adiponectin levels after Bonferroni correction and controlling for the percentage of PEA, age, annual household income and smoking. These results were consistent with the haplotype analysis. The association between the rs12495941 variant and obesity is modulated by the PEA, so that the relationship between the G allele and a higher incidence of obesity was present in those individuals within the lower PEA group. In addition we found an effect modification of obesity on the association between the ADIPOQ rs6444174 SNP and BMI so that the presence of the T allele was negatively and significantly associated with BMI only in participants with a normal weight. In this large African American cohort, ADIPOQ variants were associated with adiponectin levels in a gender-dependent manner and the relationship of some of these variants with obesity and BMI was modulated by the PEA and obesity status respectively. This suggests that the effects of these polymorphisms on adiponectin and obesity phenotypes are subject to a strong interaction with genetic and environmental factors in African American population. The online version of this article (doi:10.1186/s12881-015-0214-x) contains supplementary material, which is available to authorized users.