title: A study for association and interaction analysis to metabolic syndrome and the ESR1 gene on cardiovascular autonomic neuropathy in a Chinese Han population.
abstract: BACKGROUND
  The aim of this study was to investigate the association and interaction of metabolic syndrome (MetS) and estrogen receptor alpha 1 (ESR1) gene polymorphisms on cardiovascular autonomic neuropathy (CAN).
  
  
  METHODS
  A large-scale, population-based study was conducted to analyze the interaction of MetS and ESR1 gene polymorphisms to CAN, including a total of 1977 Chinese subjects. The most common studied single nucleotide polymorphism of ESR1 gene-rs9340799, was genotyped. Multiple logistic regression (MLR) was performed to evaluate the interaction effect of environmental variables and gene polymorphisms. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S).
  
  
  RESULTS
  After controlling potential confounders, MLR showed that significant association between MetS and CAN (p < 0.001). Interestingly, we found that the participants with MetS bearing the minor allele G had an increased CAN prevalence comparing those with allele A (p = 0.045), and a positive interaction was estimated by using RETI = 0.396 (95 % CI 0.262 to 0.598), AP = 0.216 (95 % CI -0.784 to 1.216) and S = 1.906 (95 % CI 0.905 to 4.015).
  
  
  CONCLUSIONS
  The present findings suggest that MetS is significantly associated with CAN and provide evidence for the hypothesis that MetS and ESR1 gene polymorphism (rs9340799) have interactive effects on CAN. ClinicalTrials gov Identifier NCT02461342.
authors.affiliation: Department of Endocrinology and Metabolism, Fudan University Huashan Hospital, Shanghai, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Department of Endocrinology and Metabolism, Fudan University Huashan Hospital, Shanghai, China.
authors.forename: Linuo
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065 China.
authors.forename: Zihui
authors.initials: Z
authors.lastname: Tang
keywords: Cardiovascular autonomic neuropathy; Estrogen receptor alpha gene; Interaction analysis; Metabolic syndrome