Gender-specific associations between ADIPOQ gene polymorphisms and adiponectin levels and obesity in the Jackson Heart Study cohort

Abstract

BackgroundDespite 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.MethodsGenotype 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).ResultsWe 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.ConclusionsIn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0214-x) contains supplementary material, which is available to authorized users.

The role of sex steroids in white adipose tissue adipocyte function

“…Several SNPs of the adiponectin gene (APIDOQ; rs6444174, rs1403697, rs7641507 and rs16861205) have been found to be associated with serum adiponectin levels in women but not men (Riestra et al 2015). Additionally, one of those SNPs (rs6444174) was found to be associated directly with BMI and obesity (Riestra et al 2015). Although a role of E2 in APIDOQ gene polymorphisms has not been elucidated, certainly there are differences in APIDOQ genetic determinants by gender and with respect to WAT mass.…”

“…Further studies are needed to more conclusively determine the effects of E2 on adipokine secretion. Several SNPs of the adiponectin gene (APIDOQ; rs6444174, rs1403697, rs7641507 and rs16861205) have been found to be associated with serum adiponectin levels in women but not men (Riestra et al 2015). Additionally, one of those SNPs (rs6444174) was found to be associated directly with BMI and obesity (Riestra et al 2015).…”

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“…In recent years, there have been many reports about the association between adiponectin SNPs and various diseases. Although previous studies have examined the role of adiponectin SNPs in obesity, T2D and CVD [11][12][13][14][15]37 . In this study, we did not find a significant association between the +45 T>G (rs2241766) in the ADIPOQ gene and MS in Tunisian population.…”

Single Nucleotide Polymorphisms in Adiponectin Gene Are Not Directly Associated with Increased Risk of Obstructive Sleep Apnea Syndrome in a Chinese Han Population

“…Riestra et al [11], Davis et al [20], and Ong et al [21] certified that SNPs rs12495941, rs182052, and rs16861205 were associated significantly with adiponectin levels. However, no previous studies examining the association between rs12495941, rs182052, and rs16861205 with the risk of OSAS have been published.…”

“…Additionally, a clinical study by Al Mutairi et al [10] demonstrated that adiponectin is an independent marker of disease severity in patients with OSAS. One or more single nucleotide polymorphisms (SNPs) in the ADIPOQ gene affect the synthesis and secretion of adiponectin, indicating that genetic variation within the ADIPOQ gene may be a determinant of serum adiponectin level [11], and such alterations might contribute to increased susceptibility of OSAS. Taken together, it seems reasonable to speculate that adiponectin variants are involved in the etiology of OSAS.…”