Modification of the association between the polymorphisms of adipokine genes and serum adipokine levels by vitamin D status in African Americans: The Jackson Heart Study

Abstract

BackgroundAdipokines, such as leptin and adiponectin play a central role in whole‐body homeostasis and are associated with metabolic risk factors like insulin resistance, lipid disorders and obesity. African Americans (AA) have high prevalence of vitamin D deficiency (VDD) and evidence suggests that VDD may increase metabolic risk by modifying adipokine production.ObjectiveUsing the data of 3003 participants (61.9% female, mean age 54.58 years) from the Jackson Heart Study cohort we examined whether associations between single nucleotide polymorphisms (SNP) in the human leptin (LEP) and the human leptin receptor (LEPR) genes with leptin level and SNPs in ADIPOQ gene with adiponectin level were modified by vitamin D status in adult AA.MethodsSerum 25‐hydroxy‐vitamin D< 20ng/ml was used to define VDD. In total, we selected 19, 88, and 18 tagging SNPs in LEP, LEPR and ADIPOQ gene respectively. IMPUTE2 software and reference phased data from the 1000G project were used for genotype imputation. Under the assumption that each gene represents a separate hypothesis, linear regression models were run to see the associations between SNPs with leptin and adiponectin levels adjusting for age, gender, education status, physical activity, obesity, smoking, alcohol intake, European ancestry and multiple testing separately for VDD and non‐VDD participants. Log transformed values of leptin and adiponectin were used for all analysis. A secondary analysis was done with the mean annualized 25‐hydroxy‐vitamin D derived using a cosinor model.ResultsAmong the LEP SNPs, the C allele of the rs11763517 [beta‐coefficient, β= 0.03; P=4.6×10−4] was associated with increased serum leptin levels, while the T allele of the rs17151922 [β= −0.029; P=9.0×10−5] and the A allele of the rs17151919 [β= −0.10; P=1.8 x10−16] were associated with decreased serum leptin levels in VDD participants. The rs17151919 [β= −0.098; P=7.0 x10−5] was also related with decreased leptin levels in non‐VDD participants. In addition, the A allele of the LEP SNP rs17151913 [β= 0.069; P=2.3 x10−3] was associated with increased leptin levels in them. None of the AdipoQ SNPs showed any association with adiponectin level among non‐VDD participants. However for VDD participants, carriers of the C allele of the rs4632532 [β= −0.034; P=2.3 x10−4], the T allele of the rs9842733 [β= −0.043; P=2.5 x10−3] and the G allele of the rs9877202 [β= −0.06; P=3.2 x10−5] presented decreased serum adiponectin levels. The pattern of the association remained similar in the secondary analysis.ConclusionOur findings demonstrate that the associations between adipokine SNPs and adipokine levels could be modified by vitamin D status in AA. Therefore, vitamin d status should be taken into consideration when evaluating the genetic variation of specific alleles for adipokines.Support or Funding InformationThis research was supported by the Intramural Research Program of the National Institutes of Health. The Jackson Heart Study is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities.