Is NAT2 Gene Polymorphism Associated with Vitiligo?

BACKGROUND: N-acetyltransferase-2 (NAT2) is a phase II xenobiotic enzyme that plays an important role against oxidative stress-mediated reactive oxygen species protection. Polymorphism in specific genotypes of NAT2 may lead to increase an imbalance in antioxidant systems and may influence the pathogenesis of vitiligo. We conducted this study to see the association between NAT2 gene polymorphism and risk of vitiligo. We looked into whether single-nucleotide polymorphisms (SNP) at positions 857, 481 and 590 of the coding region of the NAT2 gene play as a risk factor for vitiligo among north Indian people. METHODS: In this study, we assessed 100 patients with vitiligo and 160 healthy individuals as controls. Genomic DNA was extracted from human peripheral blood and polymerase chain reaction-restricted fragment length polymorphism was done to identify the single nucleotide polymorphism at positions 857, 481, and 590 of the coding region of the NAT2 gene. RESULTS: In this study, we observed a significant higher risk with slow acetylator genotypes of NAT2 (OR = 2.85; 95% CI = 1.68-4.84, P value < 0.001) for the vitiligo. Furthermore, in the association between NAT2 acetylator genotypes with percentage of body surface area (BSA) of disease, we observed that slow acetylator genotypes of NAT2 has significant higher risk with low grade of disease (1%-10% >11%-30% >30% of BSA). LIMITATIONS: A major limitation of this study was the small sample size and warrants further investigation on a large epidemiological study to confirm these findings. CONCLUSIONS: Our preliminary data indicate that NAT2 slow acetylator genotype exhibits significant association for the risk of vitiligo, especially in disease predisposition and initiation.

Polymorphism of glutathione S-transferase M1 and T1 genes and susceptibility to psoriasis disease: A study from North India.

BACKGROUND: Increased oxidative stress and resulting inflammation has been emphasized as a factor in the pathogenesis of many diseases including psoriasis. Glutathione S-transferases (GSTs) protect against oxidative stress, inflammation, and genotoxicity. Polymorphisms in the GST genes may lead to an imbalance in pro- and antioxidant systems resulting in the increased production of reactive oxygen species that could influence the pathogenesis of psoriasis. AIM: The aim of this study was to investigate the association between GSTs (GSTM1 and GSTT1) gene polymorphism in patients with chronic plaque psoriasis as a factor in the susceptibility and development of psoriasis. MATERIALS AND METHODS: We assessed 128 patients with psoriasis and 250 age- and sex-matched healthy controls. Genomic DNA was extracted from peripheral blood by the phenol chloroform method. The null GSTT1 and GSTM1 genotypes were identified by multiplex polymerase chain reaction (PCR) method. RESULTS: The null genotype of GSTM1 and GSTT1 was seen in 45.3% and 40.6% in psoriasis patients whereas in the controls it was 34.4% and 20.0%, respectively. A significant association was seen between the null alleles of the GSTT1 (OR = 2.74) and GSTM1 (OR = 1.58) alone or in combination with tobacco use (P < 0.001) and psoriasis risk. The presence of both null genotypes of GSTM1 and GSTT1 further increased the risk of psoriasis (OR = 3.52) when compared with the positive genotypes of GSTM1 and GSTT1. LIMITATIONS: A major limitation of this study was the small sample size. A large epidemiological study is necessary to confirm these findings. CONCLUSIONS: The null genotype of GSTT1 is a strong predisposing factor for psoriasis in North India.

Association of genetic polymorphism of glutathione S-transferase M1, T1, P1 and susceptibility to bladder cancer.

OBJECTIVE: Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens. We examined the association of the GST gene polymorphism with sporadic bladder cancer patients in Northern India. MATERIAL AND METHODS: The study constituted of 106 bladder cancer cases and 370 age-matched controls. The GSTT1 and GSTM1 null genotypes were identified by multiplex PCR and GSTP1313 A/G by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism method (PCR/RFLP). RESULTS: We observed non-significant association in null alleles of the GSTM1 (p = 0.611, OR = 1.12, 95% CI = 0.72-1.74 and GSTT1 (p = 0.135, OR = 1.45, 95% CI = 0.89-2.37) with risk of bladder cancer. However, the G/G genotype of the GSTP1 gene polymorphism was highly significant when compared to controls (p=0.000, OR = 7.12, 95% CI = 3.14-16.16). The combined analysis of the three risk genotypes demonstrated further increase in the risk of bladder cancer (p = 0.000, OR = 7.29 95% CI = 2.81-18.93). CONCLUSION: Our study demonstrated that GSTP1313 G/G polymorphism is a strong predisposing risk factor for bladder cancer. Combination of three GST genotypes association exhibiting gene-gene interaction further substantiates the increased risk of bladder cancer.

Association of vitamin D receptor gene polymorphism and risk of prostate cancer in India.

INTRODUCTION: Vitamin D plays an important role in the proliferation and differentiation of normal and malignant cells. In several studies polymorphism in the vitamin D receptor (VDR) gene has been reported to be associated with prostate cancer (CaP). The rationale of this study was to determine the association between the VDR (Fok-I) polymorphism and the risk of developing CaP. MATERIALS AND METHODS: Polymorphism was detected by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method in 128 CaP patients (age range 43-89 years) and 147 age-matched controls (age range 42-91 years). PCR products were designated as F or f allele according to the absence or presence of a restriction site. RESULTS AND CONCLUSIONS: The frequencies of the FF, Ff and ff genotypes were 60.9, 35.2 and 3.9% in CaP patients and 42.2, 46.9 and 10.9% in healthy controls, respectively. The genotype frequency distribution between CaP and the control group was statistically significant (p = 0.003). However, the distribution of genotypes was not significantly associated with the Gleason score. The present study thus demonstrates that the FF genotype (or F allele) of the VDR gene plays an important role in determining the risk of CaP and could be postulated as a good candidate genetic marker.

Genetic polymorphism of glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and susceptibility to prostate cancer in Northern India.

OBJECTIVE: To examine the association of glutathione-S-transferase (GST) gene polymorphisms in patients with sporadic prostate cancer, in a North Indian population, as GSTs are active in detoxifying a wide variety of endogenous or exogenous carcinogens, and genetic polymorphisms of GSTM1, GSTT1 and GSTP1 have been assessed to evaluate the relative risk of various cancers. PATIENTS AND METHODS: We assessed 127 patients with prostate cancer and 144 age-matched controls, all from North India. The GSTT1 and GSTM1 null genotypes were identified by multiplex polymerase chain reaction (PCR) in peripheral blood DNA samples, and GSTP1-313 A/G polymorphism was determined by PCR/restriction fragment length polymorphism. RESULTS: There was a significant association in null alleles of the GSTM1 (odds ratio 2.239, 95% confidence interval 1.37-3.65, P = 0.001) and GSTT1 (1.891, 1.089-3.282, P = 0.026) with prostate cancer risk, and in the -313 G alleles (Val) of the GSTP1 gene (2.48, 1.51-4.08, P < 0.001). The combined analysis of these three genotypes showed a further increase in the risks of prostate cancer (7.23, 2.42-22.6, P < 0.001). CONCLUSION: The GSTP1-313 G polymorphism, and null alleles of GSTM1 and GSTT1, are strong predisposing risk factors for sporadic prostate cancer in North India.

Is urokinase gene 3'-UTR polymorphism associated with prostate cancer?

Urokinase gene is believed to play a key role in tissue degradation and cell migration under various normal and pathological conditions, including cancer invasion and metastasis. It may be responsible in the development of prostate cancer (CaP), although there is lack of genetic evidence. Our aim was to study single nucleotide polymorphism (C/T) in 3'-untranslated region to investigate the possibility. DNA was extracted from blood samples of 103 CaP patients and 107 normal controls. Polymerase chain reaction (PCR) based restriction analysis was used to identify the C/T polymorphism of the urokinase gene. Significant difference in the frequency distribution of CT and TT genotypes in CaP patients as compared to normal was observed (p=0.04). Two folds risk for prostate cancer with T alleles in north Indian population was apparent. We also observed significant association for TT genotypes with higher Gleason score of tumors in CaP patients (p<0.05). A positive association was also evident in tobacco users having T alleles with risk of CaP. Our findings demonstrated a positive association of T allele of 3'UTR of urokinase gene with the risk of prostate cancer. We therefore hypothesize that C/T polymorphism may influence the etiology of CaP and is likely to become another new marker.

Polymorphism of GSTM1 and GSTT1 genes in bladder cancer: a study from North India.

The present study was conducted (1) to examine whether the GSTT1- and GSTM1-null genotypes are risk factors for bladder cancer, and (2) to study possible association of tobacco usage and age strata with genotype of these patients. This case control study was undertaken over a period of 19 months and included 106 bladder cancer patients and 182 controls; both patients and controls originated from northern part of India. The GSTT1 and GSTM1 genotypes were identified by multiplex PCR in peripheral blood DNA samples. Genotype frequencies among patients and controls were assessed and the association of the genotypes with smoking habits and gender of the patients were statistically determined by the chi(2) test. Frequencies of null genotypes in GSTT1 and GSTM1, were 16% (29/182) and 30% (54/182), respectively, in control individuals. The frequencies of GSTT1- and GSTM1-null genotypes in bladder cancer patients were 26% (28/106) and 40% (42/106), respectively. In conclusion, our study demonstrated that the null genotypes of GSTT1 and GSTM1 were substantially at higher risk for bladder carcinoma compared to the normal healthy controls. The GSTT1- and GSTM1-null genotypes did not show significant association with tobacco usage in bladder cancer patients. However, the null genotypes were statistically significant in female relative to male bladder cancer patients.