Hemant Kumar Bid

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.

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.

POLYMORPHISMS IN THE VITAMIN D RECEPTOR AND THE ANDROGEN RECEPTOR GENE ASSOCIATED WITH THE RISK OF UROLITHIASIS

Transcriptional activity of the vitamin D receptor (VDR) gene is regulated by androgen receptor (AR) gene and both are associated with renal stone formation. We examined gene polymorphisms of VDR (PCR-RFLP) and AR (GeneScan analysis) in 125 stone formers and 150 controls from north India. Genotype Ff of Fok-I and Tt of Taq-I demonstrated significantly higher risk (P<0.001, OR=3.559 and P=0.019, 1.830 respectively). Variant f allele exhibited 1.7-folds higher risk. Ff of Fok-I and Aa of Apa-I gene polymorphism showed higher risk in males only. Mean CAG repeat was significantly higher in hypercalciuric patients as compared to normocalciuric (mean=21.62 ± 3.384 vs. 20.11 ± 3.182; P=0.034). Combined effects 1.8-folds higher risk in patients with Tt genotype of Taq-I and short CAG repeat. Thus, association of FokI and TaqI VDR gene polymorphisms suggest VDR as an important genetic marker for urolithiasis. Further, patients with combination of Tt of Taq-I and short CAG repeat were at higher risk for stone formation.

Interleukin-1β and receptor antagonist (IL-1Ra) gene polymorphisms and the prediction of the risk of end-stage renal disease

Abstract Cytokines play an important role in the pathogenesis of kidney disease and its progression to end-stage renal disease (ESRD). Inflammation is regulated by the genes of the interleukin 1 (IL-1) gene cluster. Therefore, it was hypothesized that a polymorphism in this gene cluster may be associated with the risk of ESRD. Polymorphisms in the IL-1 gene cluster were examined in a cohort of 222 ESRD patients and 206 controls of similar ethnicity. These individuals were genotyped for IL-1 β (promoter –511 and exon-5 +3953) genes and a variable number of tandem repeats (VNTR) in the IL-1 receptor antagonist gene (IL-1Ra). There was significant difference in genotype frequencies between ESRD patients and control group for IL-1β (promoter region and exon-5) and IL-1Ra gene polymorphism (p<0.001, 0.006 and < 0.001, respectively). A significant difference was observed in IL-1Ra for 1/1 (410/410) and 1/2 (410/240) genotypes, and the risk for ESRD was higher in those carrying the 1/1 genotype (p=0.014, OR = 1.692, and p<0.001, OR = 0.163). Also identified was a novel, rare allele of a single copy of 86 bp in ESRD patients as compared with the controls. The haplotype ‘T-E2-1’ frequency distribution between patients and controls revealed greater than threefold risk (p=0.001, OR = 3.572, 95% CI = 1.589–8.032). Genetic linkage between the IL-1β promoter region and exon-5 and between the IL-1β promoter and IL-1Ra of IL-1 gene demonstrated a strong association among the variants in controls (D′ = 0.42, p<0.001, and D′ = 0.39, p=0.001). Thus, the three polymorphisms within the IL-1 cluster are associated with ESRD. This finding is perhaps one of the strongest associations between genotype and ESRD reported, and it suggests that the IL-1 gene cluster affects the risk of development of ESRD.

Interleukin-1 Receptor Antagonist Polymorphism in Patients with Prostate Cancer and Benign Prostatic Hyperplasia: A Case Control Study from North India

Objective: Some studies suggest that immunological components play a key role in the development of various cancers like gastric, cervical and ovarian cancers. Polymorphism in the IL-1 Ra gene has been reported to be associated with different malignant diseases. There are however, inadequate data for prostate cancer (CaP) till date. Methods: In a case control study we analyzed the polymorphism of interleukin-1 receptor antagonist (IL-1Ra) in 110 men with CaP; 92 with benign prostate hyperplasia (BPH) and 128 normal healthy controls. Genomic DNA fragments were amplified by polymerase chain reaction and visualized on 2% agarose gel. Results: The distributions of genotype and allele frequencies were significantly different between the CaP, BPH patients and the control group. In CaP and BPH patients Type B/B (410 bp) genotype is significantly dominant (51.8 and 54.3 vs. 28.9%) with greater than 3-fold risk. Type A/A (240 bp) genotype is dominant (48.4 vs. 14.5 and 19.6%) in normal controls. Allele D (325 bp) ...

Study of interleukin-1 receptor antagonist (IL-1Ra) gene polymorphism in healthy individuals from Northern India.

Cytokines play a key role in immune responses and inflammation. IL-1Ra is a naturally occurring structural variant of IL-1 that competitively inhibits receptor binding of IL-1. We have investigated the polymorphism in intron-2 of the interleukin-1 receptor antagonist gene in North Indian population. This genetic variation has been of great interest due to its possible association with a variety of human diseases primarily of epithelial and endothelial cell origin such as urolithiasis etc. Allele frequencies of the IL-1Ra polymorphism vary among different populations but there is no data till date reported from India. The present study was carried out to determine the IL-1Ra gene Polymorphism in 165 normal unrelated individuals from North India. We obtained an allelic frequency of 63.94, 30.61, 4.55, 0.90 for A, B, C and D allele and percentage of genotypes AA, BB, CC, DD, A/B, A/C, A/D and B/C were 49.7, 18.2, 2.42, 0.60, 24.2, 3.63, 0.60, 0.60 respectively. Our results suggested that the frequency and distribution of this polymorphism in India is substantially different from other populations and ethnic groups.

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.

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.

Significance of Hardy-Weinberg Equilibrium in Case Control

Accessible online at: www.karger.com/uin Dear Sir, This is in reference to the paper ‘Association of E-Cadherin Gene 3)-UTR C/T Polymorphism with Calcium Oxalate Stone Disease’ by Tsai et al. (Urol Int 2003;70:278– 281). The authors investigated the role of polymorphism and demonstrated the association of the E-cadherin gene with calcium oxalate stone disease. The article is interesting but there are some points which are not clear. We feel that the control population is not in genetic equilibrium. A simple rule is that the frequency of the heterozygous (CT) class cannot exceed 50%; however, the authors report a frequency of 88%. Applying their reported allelic frequencies to the Hardy-Weinberg calculation confirms that the genotype distribution in the control population is significantly different from the expected distribution and thus not in equilibrium. It may be, for instance, that different ethnic groups (with different allelic frequencies) do not inter-marry and equilibrium is not reached. A variety of other factors could also contribute to this non-equilibrium, such as large migrant populations. Hence to conclude the differences between the normal and the disease population cannot be addressed until this issue is resolved. If ethnicity is the source of the problem, such studies will have to be confined to single ethnic groups.