Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, United States.
Pediatric Endocrinology, Nemours Children's Clinic, Jacksonville, FL, United States.
Sci Rep. 2018 May 23;8(1):8035. doi: 10.1038/s41598-018-26230-w.
Epidemiological studies have confirmed associations of the vitamin D receptor (VDR) and vitamin D-related gene polymorphisms with adiposity and other metabolic disturbances. Those associations may be sex-specific. We evaluated the cross-sectional and longitudinal relationships between metabolic disturbances and haplotypes constructed from single nucleotide polymorphisms of VDR (BsmI:G/A: rs1544410; ApaI:A/C: rs7975232; and TaqI:G/A: rs731236) and MEGALIN (rs3755166:G/A; rs2075252:C/T and rs2228171:C/T) genes, in a sample of African-American adults. From 1,024 African Americans participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS, 2004-2013, Baltimore, MD), our analyses included 539 participants with complete genetic, baseline covariate and metabolic outcome data (at baseline and follow-up). Mean ± SD period of follow-up was 4.64 ± 0.93 y. Multivariable-adjusted Cox proportional hazards and logistic regression models were conducted. Among key findings, in men, incident hypertension was inversely related to MEGALIN (GCC), [HR = 0.45, 95% CI: 0.23-0.90, p = 0.024]. Overall, there was a direct, linear dose-response association between VDR (AAG: BAt) and MetS at baseline [OR = 1.60, 95% CI: 1.11-2.31, p = 0.012], while among men, VDR (GAA: bAT) was inversely related to baseline MetS [OR = 0.40, 95% CI: 0.19-0.81, p = 0.011]. In conclusion, VDR and MEGALIN gene variations can affect prevalent MetS and the incidence rate of hypertension, respectively, among African-American urban adults.
流行病学研究已经证实了维生素 D 受体（VDR）和维生素 D 相关基因多态性与肥胖和其他代谢紊乱之间的关联。这些关联可能具有性别特异性。我们评估了代谢紊乱与 VDR（BsmI：G/A：rs1544410；ApaI：A/C：rs7975232；和 TaqI：G/A：rs731236）和 MEGALIN（rs3755166：G/A；rs2075252：C/T 和 rs2228171：C/T）基因单核苷酸多态性构建的单体型之间的横断面和纵向关系，在一个非裔美国成年人样本中。从参加多样性在整个生命跨度中的邻里健康老龄化研究（HANDLS，2004-2013 年，巴尔的摩，MD）的 1024 名非裔美国人中，我们的分析包括 539 名具有完整遗传、基线协变量和代谢结果数据的参与者（基线和随访）。平均随访期为 4.64±0.93 年。进行了多变量调整的 Cox 比例风险和逻辑回归模型。在主要发现中，在男性中，高血压的发生率与 MEGALIN（GCC）呈负相关[HR=0.45，95%CI：0.23-0.90，p=0.024]。总体而言，VDR（AAG：BAt）与基线代谢综合征之间存在直接、线性的剂量反应关联[OR=1.60，95%CI：1.11-2.31，p=0.012]，而在男性中，VDR（GAA：bAT）与基线代谢综合征呈负相关[OR=0.40，95%CI：0.19-0.81，p=0.011]。总之，VDR 和 MEGALIN 基因变异可以分别影响非裔美国城市成年人中常见的代谢综合征和高血压的发生率。
