title: Haplotype association and synergistic effect of human aldosterone synthase (CYP11B2) gene polymorphisms causing susceptibility to essential hypertension in Indian patients.
abstract: BACKGROUND
  Aldosterone synthase (CYP11B2) is a key enzyme involved in the terminal steps of aldosterone biosynthesis. Genetic variability in CYP11B2 gene has been associated with heterogeneous aldosterone production, which can affect sodium homeostasis and thereby regulation of blood pressure. Hence, the present study was aimed to explore the single-locus variations, haplotype and epistasis patterns of CYP11B2 (C-344T, intron-2 gene conversion and Lys173Arg) gene polymorphisms, and the risk contributed by them to the development of essential hypertension (EHT).
  
  
  METHODS
  A total of 279 hypertensive patients and 200 normotensive controls were enrolled in this study. C-344T and Lys173Arg polymorphisms of CYP11B2 gene were genotyped by PCR-RFLP method and intron-2 gene conversion (IC) polymorphism by allele-specific PCR analysis.
  
  
  RESULTS
  Single-locus analysis revealed significant association of CYP11B2 C-344T and Lys173Arg polymorphisms with EHT (p < 0.05). Considering the sexes, Lys173 allele was found to be at risk for hypertension in males (OR 1.40; 95% CI = 1.01-1.96). Unphased haplotype analysis revealed H1 (T-Conv-Lys; p = 0.0017) to have significant risk for EHT, while haplotype H4 (T-Wt-Arg) had a significant protective effect. Multifactor dimensionality reduction (MDR) interaction analysis found the overall best model with C-344T and IC polymorphisms exhibiting strong synergistic effect.
  
  
  CONCLUSIONS
  The present study revealed a strong synergistic effect of CYP11B2 C-344T and IC polymorphisms causing susceptibility to EHT and haplotype H1 (-344T-Conv-Lys173) as the risk-conferring factor for hypertension predisposition.
authors.affiliation: a Department of Genetics , Osmania University , Hyderabad , India.
authors.forename: Uppuluri Mohana
authors.initials: UM
authors.lastname: Vamsi
authors.affiliation: a Department of Genetics , Osmania University , Hyderabad , India.
authors.forename: Nagalingam
authors.initials: N
authors.lastname: Swapna
authors.affiliation: a Department of Genetics , Osmania University , Hyderabad , India.
authors.forename: Gunda
authors.initials: G
authors.lastname: Padma
authors.affiliation: a Department of Genetics , Osmania University , Hyderabad , India.
authors.forename: Satti
authors.initials: S
authors.lastname: Vishnupriya
authors.affiliation: a Department of Genetics , Osmania University , Hyderabad , India.
authors.forename: Tirunilai
authors.initials: T
authors.lastname: Padma
mesh_terms: D000450:Aldosterone / Q000097:blood*; D000483:Alleles; D001794:Blood Pressure / Q000502:physiology*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D000075222:Essential Hypertension; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D015994:Incidence; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D000450:Aldosterone; D004247:DNA; D019405:Cytochrome P-450 CYP11B2
keywords: CYP11B2; MDR; epistasis; essential hypertension; haplotype; polymorphism; single locus