Impact of XPD gene polymorphism on risk of prostate cancer on north Indian population.

Prostate cancer is the second most diagnosed cancer in men next to skin cancer in the developed world. Risk of disease varies most prominently with age, ethnicity, family history, and diet. Genetic polymorphism of some genes has been implicated in increasing the risk. The XPD (Xeroderma pigmentosum group D) gene codes for a DNA helicase involved in transcription and nucleotide excision repair. The aim of this study is to evaluate the effect of XPD 751 Lys/Gln polymorphism on risk of prostate cancer on north Indian patients. Blood sample from 150 prostate cancer patients, 150 from Prostate Hyper Plasia and equal number of samples from healthy control groups was collected from North India. The polymerase chain reaction and restrictive fragment length polymorphism techniques were implemented. Statistically non-significant increase risk of prostate cancer was observed with patients having Gln/Gln genotype (OR 1.62, 95% CI).

Association of GSTM1T1 genes with COPD and prostate cancer in north Indian population.

The glutathione S-transferase (GST) family of enzymes is known to play a pivotal role in phase II of biotransformation of xenobiotics, environmental carcinogens and pharmacological drugs. The objective of the present study was to investigate the role of GSTM1 and GSTT1 null genotypes as risk factors for chronic obstructive pulmonary disease (COPD) and prostate cancer. The subjects appraised were 200 COPD cases, 150 prostate cancer cases, 150 benign prostatic hyperplasia (BPH) cases, 200 age matched controls for COPD and 172 age matched controls for prostate cancer. GSTM1 and GSTT1 null genotype was found to confer 2.5 (OR 2.45; 95% CI 1.56-3.82; P value = 0.00008) and 2.4-fold (OR 2.39; 95% CI 1.36-4.20; P value = 0.002) significant higher risk for prostate cancer. Smoking imparted a 2.2-fold significant risk of prostate cancer cases (OR 2.23; 95% CI 1.36-3.65 P value = 0.001) and twofold risk in BPH (OR 2.09; 95% CI 1.26-3.46; P value = 0.005). In case of COPD only null genotype of GSTT1 has shown 2.1-fold (OR 2.11; 95% CI 1.22-3.62; P value = 0.007) significant increased risk.

Polymorphisms in the HPC/ELAC-2 and alpha 1-antitrypsin genes that correlate with human diseases in a North Indian population.

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.

Role of genetic polymorphism of estrogen receptor-alpha gene and risk of prostate cancer in north Indian population.

Present study depicted the role of polymorphisms in estrogen receptor-alpha gene in association with prostate cancer in north Indian population. The study was performed on 157 cases of prostate cancer, 170 cases of BPH, and 170 healthy Indian males diagnosed with prostate cancer and benign prostatic hyperplasia (BPH) and healthy males as controls. Determination of polymorphism in the ER-alpha gene was done by polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis with PvuII and XbaI enzymes. An association was observed between PvuII polymorphism of ER-alpha gene and that of prostate cancer. However, there was no such association with XbaI polymorphism in ER-alpha gene.

Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population.

The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37-0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18-0.41, P < 0.001, and OR 0.18, 95% CI 0.09-0.36, P < 0.001. Our study showed D allele of ACE to be associated with marginal risk of CHD, AA genotype of FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD.

VEGF and IL-4 gene variability and its association with the risk of coronary heart disease in north Indian population.

Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor that has been shown to play a significant role in neovascularization during inflammation in atherosclerotic plaques, formation of collateral vessels to an area of ischemic myocardium and neovascularization at the edges of a myocardial infarction during its repair. Interleukin-4 (IL-4) has important role in immune cell chemotaxis, formation of endothelial cell adhesion molecules and has numerous anti-inflammatory effects which prevent the complications of atherosclerosis, the primary cause of coronary heart disease (CHD). In this study, we have analyzed the effect of 1154 A/G polymorphism of VEGF and 70 bp VNTR polymorphism of intron 3 in IL-4 genes in coronary heart disease (CHD) patients (n = 300) and their age matched controls (n = 300). To analyze polymorphic alleles, ARMS-PCR and RFLP techniques were used. Multiple logistic regression analysis was carried out with statistical software. GG genotype was associated with a decreased risk of development of CHD (OR 0.22, 95% CI 0.12-0.38, P < 0.001). However, A allele showed an increased risk whereas G allele decreased the risk of CHD with diabetes mellitus, hypertension, chronic mental stress and positive familial history of myocardial infarction (MI)/CHD. GG genotype was found to have protective effect with alcohol intake (OR 0.34, 95% CI 0.14-0.82, P < 0.01) and central obesity (OR 0.15, 95% CI 0.04-0.56, P < 0.001). GG genotype of VEGF has also shown significant association with IL-4 (P2P2 and P1P2) genotypes.

Association between IL6 gene polymorphism and the risk of chronic obstructive pulmonary disease in the north Indian population.

Interleukin-6 (IL6) is encoded by the IL6 gene in human and acts as pro-inflammatory cytokine and an anti-inflammatory cytokine. Recent studies established that IL6 substantially contribute in the diagnosed of systemic inflammation for the patients suffering from lung diseases such as chronic obstructive pulmonary disease (COPD). Thereof, this work aimed to investigate the protagonist of IL6 (-174 G/C) genotypes as an essential risk factor for COPD in north Indian population. In the study, a total of 200 clinically diagnosed patients with COPD were selected against 200 patients. Statistical analysis reveleaed that there was no significant association between the IL6 -174 G/C genetic polymorphism and the risk of COPD (P>0.05).

CYP17 gene polymorphism and its association in north Indian prostate cancer patients.

BACKGROUND: The CYP17 gene codes for the cytochrome P450c17a enzyme, which mediates two key steps in sex steroid synthesis In this study, the association between CYP17 polymorphism and the risk of prostate cancer in comparison to benign prostatic hyperplasia (BPH) in a north Indian population was investigated. PATIENTS AND METHODS: This study included 157 prostate cancer patients and 170 BPH patients as controls. A 451-bp fragment encompassing the polymorphic site was amplified by PCR and treated with the restriction enzyme MspA1. The undigested allele was recognized as A1 and the MspA1-digested variant allele was designated as the A2 allele. RESULTS: Men with the A2/A2 CYP17 genotype had an increased risk of prostate cancer (OR=3.56; 95% CI=1.49-8.53; p=0.004) compared with those with the A1/A1 genotype. A significantly increased risk of prostate cancer was also found in smokers as well as non-vegetarians by four-fold as compared to their counterparts. There was a significant association between the CYP17 genotype and the tumour status (stage) of prostate cancer. The A2 allele showed a 1.90- (95% CI=1.09-3.32; p=0.02) and a 1.51- (95% CI=1.08-2.13; p=0.017) fold increased risk of prostate cancer in localized and metastatic prostate cancer cases respectively. CONCLUSION: The A2 allele of the CYP17 polymorphism is associated with an increased risk of prostate cancer and has a role in the development of prostate cancer in smokers and non-vegetarians.

Insertion/deletion polymorphism of angiotensin-converting enzyme and chronic obstructive pulmonary disease: A case-control study on north Indian population.

This research aimed to explore the ACE (insertion/deletion) gene association as key factor for chronic obstructive pulmonary disease (COPD) development in north Indian population. A total of 200 clinically diagnosed patients with COPD were selected against 200 healthy individuals. Genetic variations of ACE (insertion/deletion) were evaluated by using polymerase chain reaction techniques. Smoker showed higher risk of COPD (OR=1.67, 95% CI=1.12-2.48, P=0.012). Present results revealed the positive association between the DD genotype and the risk of COPD (OR= 2.14, 95% CI=1.22-3.78, P=0.006). Among smokers, DD genotype showed statistically significant association with increased risk of COPD (OR=3.10, 95% CI= 1.50-6.47, P=0.001).