Gene-Gene interactions of CYP2D6 (*2, *4, *10) and GST (T1, M1, P1) variants in Essential Hypertensive Jat Sikh patients.

Tarandeep Kaur; Gursatej Gandhi

Tarandeep Kaur LV Prasad Eye Institute, Hyderabad, India
Gursatej Gandhi Guru Nanak Dev University, Amritsar, India

Keywords: Multifactor dimensionality reduction; CART; metabolic genotypes; Epistatic interactions., Hypertension, Jat Sikh

Abstract

Objective: To investigate interactions, if any, among six functional SNPs of metabolic genes viz. CYP2D6 (*2, *4, *10) and GST (T1, M1, P1) in essential hypertensive Jat Sikh north Indian patients.

Methods: Unrelated 200 essential hypertensive patients and 200 normotensive healthy individuals were genotyped for CYP2D6 (*2, *4, *10) and GST (T1, M1, P1; 313A>G) polymorphisms using PCR-RFLP analysis. Association of disease-risk with SNPs was ascertained by logistic regression analysis. High order gene–interactions were ascertained by performing multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses.

Results: The patient and control groups differed significantly in the genotype frequencies of GSTP1 polymorphisms (p<0.0001). The crude odds ratio analysis divulged that individuals with the heterozygous genotypes in CYP2D6*4 (p=0.0280), *10 (p=0.0002) and GSTP1 (p=0.0001) genes have 1.60 to 4.50 folds, and those with the homozygous mutant genotypes in CYP2D6*4 (p=0.0019) and GSTP1 (p=0.0001) genes have3.21-7.02 folds likelihood for hypertension. MDR analysis revealed the best predictive epistatic interaction among CYP2D6*4, *10 and GSTP1 SNPs for disease as 24% patients were heterozygous for these genotypes (OR=7.3889; 95% CI= 4.7417-11.5141). The decision tree by CART analysis further revealed GSTP1 as a major predictor for hypertension risk.

Conclusion: Interactions of heterozygous genotypes of CYP2D6*4, *10 and GSTP1 were revealed as significantly contributing towards hypertension with GSTP1 as a major predictor for hypertension risk in Jat Sikh patients.