title: Epistatic interactions in idiopathic pulmonary arterial hypertension.
abstract: BACKGROUND
  Idiopathic pulmonary arterial hypertension (IPAH) is a poorly understood complex disorder, which results in progressive remodeling of the pulmonary artery that ultimately leads to right ventricular failure. A two-hit hypothesis has been implicated in pathogenesis of IPAH, according to which the vascular abnormalities characteristic of PAH are triggered by the accumulation of genetic and/or environmental insults in an already existing genetic background. The multifactor dimensionality reduction (MDR) analysis is a statistical method used to identify gene-gene interaction or epistasis and gene-environment interactions that are associated with a particular disease. The MDR method collapses high-dimensional genetic data into a single dimension, thus permitting interactions to be detected in relatively small sample sizes.
  
  
  OBJECTIVE
  To identify and characterize polymorphisms/genes that increases the susceptibility to IPAH using MDR analysis.
  
  
  METHODS
  A total of 77 IPAH patients and 100 controls were genotyped for eight polymorphisms of five genes (5HTT, EDN1, NOS3, ALK-1, and PPAR-γ2). MDR method was adopted to determine gene-gene interactions that increase the risk of IPAH.
  
  
  RESULTS
  With MDR method, the single-locus model of 5HTT (L/S) polymorphism and the combination of 5HTT(L/S), EDN1(K198N), and NOS3(G894T) polymorphisms in the three-locus model were attributed to be the best models for predicting susceptibility to IPAH, with a P value of 0.05.
  
  
  CONCLUSIONS
  MDR method can be useful in understanding the role of epistatic and gene-environmental interactions in pathogenesis of IPAH.
authors: Department of Genetics, Osmania University, Hyderabad, Andhra Pradesh, India.
authors: Shivani
authors: S
authors: Vadapalli
authors: M L
authors: ML
authors: Satyanarayana
authors: K L
authors: KL
authors: Chaitra
authors: H Surekh
authors: HS
authors: Rani
authors: B K S
authors: BK
authors: Sastry
authors: Pratibha
authors: P
authors: Nallari