title: Emilin1 gene and essential hypertension: a two-stage association study in northern Han Chinese population.
abstract: BACKGROUND
  Elastogenesis of elastic extracellular matrix (ECM) which was recognized as a major component of blood vessels has been believed for a long time to play only a passive role in the dynamic vascular changes of typical hypertension. Emilin1 gene participated in the transcription of ECM's formation and was recognized to modulate links TGF-beta maturation to blood pressure homeostasis in animal study. Recently relevant advances urge further researches to investigate the role of Emilin1 gene in regulating TGF-beta signals involved in elastogenesis and vascular cell defects of essential hypertension (EH).
  
  
  METHODS
  We designed a two-stage case-control study and selected three single nucleotide polymorphisms (SNPs), rs3754734, rs2011616 and rs2304682 from the HapMap database, which covered Emilin1 gene. Totally 2,586 subjects were recruited from the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA). In stage 1, all the three SNPs of the Emilin1 gene were genotyped and tested within a subsample including 503 cases and 490 controls, significant SNPs would enter into stage 2 including 814 cases with hypertension and 779 controls and analyze on the basis of testing total 2,586 subjects.
  
  
  RESULTS
  In stage 1, single locus analyses showed that SNPs rs3754734 and rs2011616 had significant association with EH (P < 0.05). In stage 2, weak association for dominant model were observed by age stratification and odds ratio (ORs) of TG+GG vs. TT of rs3754734 were 0.768 (0.584-1.009), 0.985 (0.735-1.320) and 1.346 (1.003-1.806) in < 50, 50-59 and > or = 60 years group and ORs of GA+AA vs. GG of rs2011616 were 0.745 (0.568-0.977), 1.013 (0.758-1.353) and 1.437 (1.072-1.926) in < 50, 50-59 and > or = 60 years group respectively. Accordingly, significant interactions were detected between genotypes of rs3754734 and rs2011616 and age for EH, and ORs were 1.758 (1.180-2.620), P = 0.006 and 1.903 (1.281-2.825), P = 0.001, respectively. Results of haplotypes analysis showed that there weren't any haplotypes associated with EH directly, but the interaction of hap2 (GA) and age-group found to be significant after being adjusted for the covariates, OR was 1.220 (1.031-1.444), P value was 0.020.
  
  
  CONCLUSIONS
  Our findings don't support positive association of Emilin1 gene with EH, but the interaction of age and genotype variation of rs3754734 and rs2011616 might increase the risk to hypertension.
authors.affiliation: Department of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College P eople's Republic of China, No, 167 Beilishi Rd, Beijing 100037, PR China. sc100@126.com
authors.forename: Chong
authors.initials: C
authors.lastname: Shen
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Lu
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.forename: Liping
authors.initials: L
authors.lastname: Hou
authors.forename: Laiyuan
authors.initials: L
authors.lastname: Wang
authors.forename: Shufeng
authors.initials: S
authors.lastname: Chen
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Huang
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D008562:Membrane Glycoproteins; C030340:elastin microfibril interface located protein