title: Novel genetic variation in exon 28 of FBN1 gene is associated with essential hypertension.
abstract: BACKGROUND
  Recently, fibrillin-1 (FBN1) was reported to play an important role in maintaining the physiological arterial stiffness of essential hypertension (EH). Here, we designed a two-stage case-control study to investigate whether the FBN1 gene harbored any genetic variations associated with EH.
  
  
  METHODS
  In stage 1, six candidate single-nucleotide polymorphisms (SNPs) of the FBN1 gene were genotyped and tested in 503 cases and 490 controls. SNPs associated with EH (P < 0.05) in stage 1 would be genotyped in stage 2 (814 cases and 779 controls), and analyzed in all the individuals by allele, genotype, haplotype, and diplotype. A meta-analysis was performed and inverse-variance method with random effect model was employed to estimate combined odds ratio (OR) and its 95% confidence interval (CI) for the identified SNPs.
  
  
  RESULTS
  In stage 1, rs140598 and rs6493333 had statistical association with EH (P < 0.05) and enter stage 2. Multiple logistic regression analysis confirmed that rs140598 but not rs6493333 significantly associated with EH in stage 2 sample. Meta-analysis showed that there was nearly no heterogeneity (I(2) = 0) of genetic variance of rs140598 in the two stages, and the associations of rs140598 in all three genetic models presented statistical significance. Further haplotype analyses showed that the Hap2 (G-C) might decreased the risk of EH when compared with reference haplotype Hap1 (C-C), adjusted OR (95%CI) was 0.823 (0.715-0.948), P = 0.006.
  
  
  CONCLUSIONS
  Our finding suggested there is a significant association of rs140598 of FBN1 gene with EH and further replication in other population for association study or prospective study should be warranted.
authors.affiliation: Division of Population Genetics, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Chong
authors.initials: C
authors.lastname: Shen
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Lu
authors.forename: Laiyuan
authors.initials: L
authors.lastname: Wang
authors.forename: Shufeng
authors.initials: S
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Li
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Huang
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines