| ORIGINAL ARTICLE |
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| Year : 2012 | Volume
: 18
| Issue : 1 | Page : 56-61 |
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Epistatic interactions in idiopathic pulmonary arterial hypertension
Shivani Vadapalli1, ML Satyanarayana1, KL Chaitra1, H Surekh Rani1, B.K.S. Sastry2, Pratibha Nallari1
1 Department of Genetics, Osmania University, Hyderabad, Andhra Pradesh, India
2 Department of Cardiology, CARE Hospitals, Hyderabad, Andhra Pradesh, India
Correspondence Address:
Pratibha Nallari
Department of Genetics, Osmania University, Hyderabad - 500 004, Andhra Pradesh
India
 Source of Support: None, Conflict of Interest: None  | 2 |
DOI: 10.4103/0971-6866.96652
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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.
Aim: To identify and characterize polymorphisms/genes that increases the susceptibility to IPAH using MDR analysis.
Materials and 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.
Conclusion: MDR method can be useful in understanding the role of epistatic and gene-environmental interactions in pathogenesis of IPAH. |
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