Biomedical subjects

Rama Devi Mittal

Publications and source records attributed to Rama Devi Mittal.

15 recordsLinked to original sources

PubMed2007

Association of interleukin (IL)-4 intron-3 and IL-6 -174 G/C gene polymorphism with susceptibility to end-stage renal disease.

Earlier studies suggest that end-stage renal disease (ESRD) is associated with inflammatory state and have become a major cause of morbidity and mortality worldwide. This study speculated the role of interleukins (IL)-2, -4, and -6 cytokines gene polymorphism with risk of susceptibility to ESRD. Polymorphism in IL-2 (-330 T/G, polymerase chain reaction [PCR]-restriction fragment length polymorphism), IL-4 (intron-3, variable number of tandem repeat, variable number tandem repeats analysis), and IL-6 (-174 G/C, amplification refractory mutation system, i.e. ARMS-PCR) were genotyped in 193 ESRD patients and 180 controls. Significant difference was observed in genotype frequencies of IL-4 and IL-6 between ESRD patients and control group (p<0.001 and p=0.032, respectively). Patients had higher frequency of homozygous B2B2 genotype (IL-4) than controls (62.7% vs 46.7) and GG genotype of IL-6 (73.1% vs 60.6%). The genotypic frequencies of IL-2 were comparable in patients and controls (p=0.102). Significant association of IL-4 was also observed in patients with glomerulonephritis (p=0.001). Combination of low IL-4 and high IL-6 genotypes were significantly associated with ESRD showing the highest risk, i.e. >threefolds risk (odds ratio=3.48, 95%CI=1.88-6.42; p < 0.001) among the four possible combinations taking high IL-4 and low IL-6 as reference. Our study suggests that polymorphism in IL-4 and IL-6 may be associated with susceptibility to ESRD. Further, combined analysis implicated a higher risk in ESRD patients with low IL-4 and high IL-6 producing genotypes. This study provided the basis for defined anti-inflammatory approaches to limit renal disease progression.

Adolescent↗

PubMed2006

Correlation between a gene polymorphism of tumor necrosis factor-alpha (G/A) and end-stage renal disease: a pilot study from north India.

BACKGROUND: Patients with chronic kidney disease manifest an inflammatory state in comparison to healthy individuals. Tumor necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory cytokine involved in initiation and progression of renal injury. We examined the 2-promoter region polymorphism of TNF-alpha gene G to A at -308 and at +488 sites in end-stage renal disease (ESRD) subjects. METHODS: The TNF-alpha -308 G/A and +488 G/A polymorphisms were genotyped in 231 patients aged 36.5+/-10, and in 180 matched controls (34.96+/-11.3) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system (ARMS-PCR) method, respectively. RESULTS: The genotypic distribution of TNF-alpha -308 and +488 were significantly different between patients and controls (P<0.001 and P<0.006), respectively. The AA genotype was more frequent in ESRD patients than controls for both the sites (42% vs. 2.8% and 17.3% vs. 2.2%), respectively. The allelic frequency of TNF-alpha A was also higher in cases than in controls for both the sites (P<0.001; OR=2.96; 95% CI=2.228-3.945 and P<0.013; OR=1.422; 95% CI=1.078-1.876). Significant difference was observed for haplotype frequency distribution between ESRD patients and controls and 'A-G#' haplotype showed >9-fold higher risk (OR=9.886, 95% CI=4.408-22.172). The two polymorphisms were in linkage disequilibrium in the control group (D'=0.8047, P<0.001). CONCLUSION: Both the variants of TNF-alpha (-308 and +488) polymorphism had significant association and may thus be a strong predisposing risk factor for ESRD in a cohort of north Indian population. Further, individuals with haplotypes A-G# may be at higher risk for ESRD.

Adenosine↗

PubMed2006

Genetic association of interleukin-1beta and receptor antagonist (IL-1Ra) gene polymorphism with allograft function in renal transplant patients.

Cytokines are known to be important mediators during renal graft outcome. The present study was therefore, conducted to determine the impact of IL-1beta and its receptor antagonist polymorphism on allograft outcome. We evaluated single nucleotide polymorphism (SNPs) in interleukin-1 gene cluster, IL-1beta (promoter region -511 and exon-5 +3954) and IL-1Ra (86-bp VNTR) in 136 renal transplant recipients and 150 normal healthy controls by polymerase chain restriction based (PCR-RFLP) analysis. Recipients were HLA matched and clinically characterized including delayed graft function (DGF), rejection episode (RE) and stable graft function (SGF). Haplotypes and linkage disequilibrium (LD) were determined using SNPAnalyzer software. Significant difference was observed for the frequency distribution of the three sites of IL-1 gene among patients and controls (p<0.001, 0.022 and <0.001 respectively). When RE and DGF were compared to SGF, only IL-1Ra showed significant differences among RE and SGF (p=0.014) and DGF and SGF (p=0.020). The presence of 1/2 genotype showed 18 folds risk in RE and 10 folds in DGF (OR=18.000 and OR=10.667 respectively). The majority of recipients with SGF had 1-4 HLA mismatch whereas RE had 5-8 mismatches. Risk for rejection increased >6 folds (OR=6.571; p<0.01) for 5-8 mismatches. Haplotypes constructed with the combination of three polymorphisms in IL-1 gene cluster showed significant difference between RE and SGF group. LD value for IL-1beta (promoter region) and IL-1Ra and IL-1beta promoter and exon-5 gene in the control group indicated strong association among the variants (D'=0.37, p<0.0001 and D'=0.29, p=0.002). Our study demonstrate that genetically determined low production of IL-1Ra may be a risk factor for RE and DGF and that IL-1beta/IL-1Ra haplotype influences the impact of allograft outcome. These findings may significantly abet in better perception of the survival of the graft.

Adolescent↗

PubMed2006

Association of interleukin-1Ra gene polymorphism in patients with bladder cancer: case control study from North India.

OBJECTIVES: To evaluate whether polymorphism of interleukin (IL)-1beta gene (exon 5 and promoter region) and IL-1 receptor antagonist (Ra), 86-bp variable number tandem repeat, are associated with transitional cell carcinoma of the urinary bladder, because cytokines have been hypothesized to be important in cancer development. METHODS: The study included 120 patients with bladder cancer (age range 32 to 69 years) and 150 age-matched controls (age range 25 to 62 years). The polymorphisms were identified by polymerase chain reaction/restriction fragment length polymorphism method and IL-1Ra polymorphism by variable number of identical tandem repeat analysis. Genotype distribution and allelic frequencies between patients and controls were compared. RESULTS: A significant difference was found in the frequency distribution of the IL-1Ra gene polymorphism in patients with bladder cancer compared with the normal control group (P < 0.001), but no difference was found in the frequencies of the IL-1beta promoter region and exon 5 genotypes between patients with bladder cancer and controls (P = 0.112 and P = 0.953, respectively). CONCLUSIONS: This is perhaps the first report on polymorphic changes in gene encoding IL-1Ra in patients with bladder cancer from India. Our data suggest that IL-1Ra intron 2 polymorphism seems to play a prominent role among the IL-1 gene cluster with respect to bladder cancer, and the association studies appear to be plausible in determining the cancer susceptibility and risk.

Adult↗

PubMed2006

Association of Urokinase Gene 3'-UTR T/C polymorphism with bladder cancer.

INTRODUCTION: Bladder cancer is a disease characterized by multiple recurrences. Some investigators assume urokinase to be involved in the causation of bladder cancer, although there is lack of genetic evidence. Our aim was to evaluate whether polymorphism of the urokinase gene is associated with transitional cell carcinoma (TCC) of the urinary bladder. MATERIALS AND METHODS: The study included 100 patients (mean age 62.5 +/- 10.2 years) with TCC of urinary bladder and 150 healthy controls (mean age 60 +/- 11.5 years) living in the same area. Polymerase chain reaction (PCR)-based restriction analysis was used to identify the C/T polymorphism of the urokinase gene. Genotyping distribution and allelic frequencies between patients and controls were compared. RESULTS AND CONCLUSION: There was a significant difference in the frequency distribution of the urokinase gene 3'-UTR C/T polymorphism in bladder cancer patients as compared to the normal control group (p < 0.05), but no significant difference in allelic frequencies or in carriage rates between bladder cancer patients and normal controls were observed. Our study suggests that urokinase gene polymorphism may be associated with bladder cancer and can thus serve as a potential genetic marker in screening for the possible causes of bladder cancer. Perhaps analysis of patients with superficial bladder TCC and mutated urokinase might help clarify this aspect in large cohort studies in different populations.

3' Untranslated Regions↗

PubMed2005

Association of vitamin-D and calcitonin receptor gene polymorphism in paediatric nephrolithiasis.

We investigated the role of vitamin-D receptor gene (VDR) and calcitonin receptor (CTR) gene polymorphism in childhood nephrolithiasis in the north Indian population. A control group of 60 healthy paediatric individuals (age range 4-16 years) and 50 paediatric patients (age range 2-14 years) with kidney stones were examined. Polymorphism in both genes (VDR and CTR) was detected by using PCR-based restriction analysis. There was a statistically significant difference between the two groups for the genotypes of the VDR gene Fok-I polymorphism (P =0.007) and the CTR gene (P =0.048) polymorphism. The odds ratio (95% Confidence Interval) for the C allele in those at risk of stone disease was 1.83 (0.82-4.09) in VDR gene polymorphism and 1.99 (0.90-4.39) in the case of CTR gene polymorphism. Our results suggest that the effects of VDR (Fok-I) and CTR gene polymorphism contribute to the understanding of the pathogenesis of urinary calculi. It is also suggestive of a potential candidate gene in the search for genetic causes of paediatric calcium oxalate nephrolithiasis.

Adolescent↗

PubMed2005

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.

Carcinoma, Transitional Cell↗

PubMed2005

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.

Genetic Predisposition to Disease↗

PubMed2005

Internet resources and urology.

INTRODUCTION: The Internet is a massive expanding body of information, which is likely to play a significant role for clinicians and researchers in patient health care across the world. Since its inception in December 1969, the Internet has grown rapidly and is anticipated to expand 100% in the coming next few years. This review illustrates to the urologists many uses of the Internet and hopefully provides a useful resource for professional and personal use. Our aim was to explain the origin, functions, use and impact of the Internet and to provide a list of important website addresses related to urology. MATERIALS AND METHODS: We undertook a detail scan of the Internet and identified a large number of websites pertaining to urology. The sites were then thoroughly searched to evaluate their potential usefulness to urology clinicians and researchers. Lists of website addresses were then compiled according to specific sub-areas of urology. RESULTS AND CONCLUSION: This overview of the Internet and a compilation of important website addresses is expected to stimulate and instruct urologists in the use of the Web in patient health care delivery and research.

Internet↗

PubMed2005

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.

Gene Frequency↗

PubMed2005

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.

3' Untranslated Regions↗

PubMed2004

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.

Adult↗

PubMed2004

Gut-inhabiting bacterium Oxalobacter formigenes: role in calcium oxalate urolithiasis.

Oxalate plays a crucial role in the formation of most renal stones. Oxalate is a common constituent of most diets and a byproduct of metabolism, and if it is not sufficiently degraded, it may accumulate. In humans, gut bacteria degrade 70 to 100 mg of oxalate per day. Oxalobacter formigenes is a gram-negative, obligately anaerobic, rod-shaped bacterium with an absolute requirement for oxalate. Although not present in the gut at birth, it quickly colonizes most children, and there is epidemiologic evidence that its absence is a risk factor in calcium oxalate stone formation. We review the metabolism, genetics, and identification of this organism and its possible therapeutic role in recurrent stone-forming patients.

Animals↗

PubMedDate not supplied

Y chromosome micro-deletions in idiopathic infertility from Northern India.

Azoospermia factor locus (AZF) is assumed to contain the genes responsible for spermatogenesis. Deletions in these genes are thought to be pathologically involved in some cases of male infertility associated with azoospermia or oligozoospermia. An attempt was made to establish the prevalence of micro-deletions on the Y chromosome in 79 infertile North Indians with azoospermia and oligozoospermia. Detail clinical examinations as well as endocrinological parameters were also done. Polymerase chain reaction (PCR) micro-deletion analysis was done in 79 infertile men. For this, genomic DNA was extracted from the peripheral blood. Seven sets of primers were used encompassing AZFa, AZFb and AZFc regions. Micro-deletions in five of the 79 cases (6.3%) showed deletions of at least one of the STS markers. Deletions were detected with known and unknown aetiology and at least in one of the infertile male with varicocele. AZF micro-deletions seen in idiopathic infertile males suggest the need for molecular screening in non-idiopathic cases.

Chromosome Deletion↗

PubMedDate not supplied

Evaluating polymorphic status of glutathione-S-transferase genes in blood and tissue samples of prostate cancer patients.

Prostate cancer is the most common urologic malignancy, involving multiple factors. There is evidence that suggests that detoxification enzymes and growth factors may play a role in its development . The glutathione S-transferase (GST) enzymes detoxify several carcinogens and genetic polymorphisms in GSTM1, T1, and P1 (Ile105Val) have been reported to be associated with prostate cancer, mainly from blood samples. As expression studies suggest differential expression of different genes in tissues, we hypothesize that polymorphic status may be differently expressed for GSTM1, GSTT1 and GSTP1 gene in blood and tissues of prostate cancer patients and BPH controls, impacting on the development of prostate cancer. To study this, we extracted DNA from blood and tissue samples of patients undergoing biopsy procedures or transurethral resection of prostate tissue. Genotyping for GSTM1 and T1 was conducted by multiplex PCR and for GSTP1 by the PCR-RFLP method. Our results suggested no significant differences in frequency distribution of M1, T1 and P1 between blood and tissue samples of patients and controls, but in a few patients differences in polymorphic status were observed. However, they were not significant. Furthermore, we observed a significant risk of prostate cancer with null allele of GSTT1 and GSTM1 and Val allele of GSTP1, supporting our previous findings. A study with large sample size using radical prostectomy tissue now needs to be performed to attain a specific conclusion.

Aged↗