title: Polymorphisms in the HPC/ELAC-2 and alpha 1-antitrypsin genes that correlate with human diseases in a North Indian population.
abstract: Two genes HPC/ELAC-2 and AAT were studied in north Indian population. HPC/ELAC-2 was studied in prostate cancer cases and AAT was studied in COPD patients. HPC/ELAC-2 is considered as an important cancer-susceptibility gene in prostate cancer. There are two common polymorphisms of this gene, i.e., Ser217Leu and Ala541Thr. Alpha 1 antitrypsin is a highly polymorphic anti-elastase enzyme, especially active in the protection of alveoli and liver. In the present study, we observed the distribution of two deficient alleles PiZ and Pi S in COPD patients. We extracted the DNA from 157 prostate cancer cases, 200 COPD patients, 170 BPH and 370 healthy controls. The polymorphisms were studied by PCR-RFLP technique. The mutant genotype (Leu/Leu) of HPC/ELAC-2 was present in 9.6, 7.6 and 5.9% of BPH, cancer cases and healthy controls, respectively. Higher risk of Ser/Leu as well as Leu/Leu had shown when compared to healthy controls. That was about 1.5 and 1.7-fold (OR = 1.55; 95% CI = 0.96-2.51; OR = 1.70; 95% CI = 0.74-3.92), respectively. Risk was found to be increased in smokers and those consuming non-vegetarian diet. Our results suggest that the HPC/ELAC-2 polymorphisms, especially in localized cases, could help to predict prostate cancer risk and confirm its high prevalence of the leu/leu allele in north Indian population. Considering heterozygous PiZ genotype, we obtained an OR of 3.82 (P = 0.03). Multivariate analysis adjusted by age sex and drinking habit showed 4.15-fold increased risk for COPD in PiZ heterozygous individuals. No increased risk was observed in the individuals carrying PiS alleles.
authors.affiliation: Department of Biotechnology, Panjab University, Chandigarh 160014, India.
authors.forename: Ranbir C
authors.initials: RC
authors.lastname: Sobti
authors.forename: Hitender
authors.initials: H
authors.lastname: Thakur
authors.forename: Lipsy
authors.initials: L
authors.lastname: Gupta
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Janmeja
authors.forename: Amlesh
authors.initials: A
authors.lastname: Seth
authors.forename: Sharwan K
authors.initials: SK
authors.lastname: Singh
mesh_terms: D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: C421605:ELAC2 protein, human; D009363:Neoplasm Proteins; D000515:alpha 1-Antitrypsin