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Background: Interleukin (IL)-8 -251 T/A and IL-10 (-1082 G/A and -819/592 C/T) polymorphisms and their expression may influence gastritis, atrophy, intestinal metaplasia (IM) and gastric cancer (GC) following H. pylori infection., Methods: Genotyping of these genes was performed (ASO-PCR) in 200, 182 and 250 with GC, functional dyspepsia (FD) and healthy controls (HC), respectively. Anti-H. pylori IgG-antibody was tested in all and serums IL-8 and IL-10 were measured randomly in 60 subjects of each group by ELISA., Results: Pro-(IL-8)-251 AA and anti-inflammatory (IL-10)-819 TT genotypes were commoner among GC than HC (p = 0.023, OR 1.86 [1.09-3.2] and p = 0.020, OR 2.0 [1.11-3.5]) but comparable with FD. IL-8 AA and IL-10-819 T allele carriage was also commoner in H. pylori-infected GC than HC (p = 0.011, OR 2.47 [1.23-5.0], and p = 0.018, OR 2.3 (1.16-4.59). IL-10-1082 G/A genotype and haplotypes (ACC, GCC, ATA and GTA) were comparable in all groups. Circulating levels of IL-8 and IL-10 were higher among GC than HC but comparable to FD (IL-8; 57.64 [6.44-319.46] vs. 54.35 [4.24-318.96] and 26.33 [4.67-304.54] pg/ml, p < 0.001 and IL-10; 15.47 [1.01-270.87] vs. 12.28 [0.96-64.88] and 3.79 [1.24-56.65], p < 0.001 for GC vs. HC). IL-8/IL-10 ratio was lower among GC than HC but higher than FD (3.7 [0.18-38.41] vs. 6.59 [0.98-130.2], p < 0.001 and 4.22 [0.15-61.4], p < 0.01). Circulating levels of IL-8, IL-10 and IL-8/lL-10 ratios were different among H. pylori-infected and non-infected GC than HC (p < 0.001, p < 0.001 and p < 0.01)., Conclusions: Pro-(IL-8)-251 T/A and anti-inflammatory (IL-10)-819 C/T gene polymorphisms and their circulating levels may play a role in H. pylori-associated gastric carcinogenesis in northern India.

Objective: Genome-wide association studies have confirmed association of TP63C/T rs710521, TERTC/T rs2736098, and SLC14A1C/T rs17674580 gene variants with susceptibility to bladder cancer (BC) in European and White population. However, the risk conferred for BC for above gene variants in North Indians is unknown. We therefore, studied the association of TP63C/T, TERTC/T, and SLC14A1C/T single nucleotide polymorphisms (SNPs) with a risk of BC susceptibility in North Indian cohort., Material and Methods: In histologically confirmed 225 BC cases and 240 healthy controls, 3 SNPs were genotyped by real-time polymerase chain reaction. To evaluate the SNP effects on BC susceptibility, odds ratio (OR) and CI 95% were calculated., Results: In case of TP63C/T, the variant genotype (TT) showed significant reduced risk for BC (P = 0.045, OR = 0.53). Combining heterozygous and variant genotypes also demonstrated reduced risk for BC (P< 0.001, OR = 0.54). In case of TERTC/T, heterozygous genotype (CT) as well as variant genotype (TT) showed significant risk for BC susceptibility (P = 0.031, OR = 1.77 and P = 0.004, OR = 2.78, respectively) along with T allelic level (P<0.001, OR = 4.19). Furthermore, in case of SLC14A1C/T gene polymorphism, the variant genotype (TT) showed significant high risk for BC susceptibility (P = 0.006; OR = 3.01) along with variant T allelic level (P = 0.003, OR = 1.52). Interestingly, smoking was also found to modulate risks for BC in case of TERT and SLC14A1 variant genotype (TT). Further clinical confounding factor, namely, tumor grade/stage level of cases, supports the genotypic data with TERT and SLC14A1 showing a risk for BC susceptibility., Conclusion: Our results suggested that polymorphism in TERTC/T and SLC14A1C/T confirmed high risk for BC in North Indian population. However, TP63C/T showed reduced risk of BC susceptibility. More replicate studies with large sample size and diverse ethnicity are required to validate these observations., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To test the hypothesis that sexual dysfunction in elderly men with benign prostatic hyperplasia leads to prostatic inflammation, diagnosed by prostatic fluid interleukin-8 (IL-8), which lowers the positive predictive value of prostate-specific antigen (PSA)., Methods: Overall, 160 men with lower urinary tract symptoms between 50 and 75 years of age with an elevated PSA level of more than 4 ng/ml with normal digital rectal examination and 50 age-matched controls with normal PSA level were prospectively evaluated for prostatic fluid IL-8 levels. Erectile dysfunction was measured by self-administered questionnaire of the Sexual Health Inventory for Men. Total and free serum PSA levels and IL-8 in prostatic fluid were measured 6 to 8 weeks after a course of 400mg of ofloxacin and 20mg of piroxicam given daily for 2 weeks. Transrectal ultrasonography-guided biopsy was done only when PSA level did not decrease less than 4 ng/ml., Results: Mean ages of patients and controls were 63.18 (standard deviation [SD]±7.10) and 60.18 (SD+6.02) years, respectively. Mean concentration of IL-8 in prostatic fluid of the patients was significantly higher, i.e., 6678 pg/ml (SD±1985.7) than in control, i.e., 1543 pg/ml (SD±375.7) (P<0.001). Following anti-inflammatory treatment, there was a significant decrease in the mean level of IL-8 from baseline to 5622 pg/ml (SD±1870.66) (P<0.001). Corresponding to this, a significant decrease was noted in total PSA levels to less than 4 ng/ml in 105 (65.62%) patients. Men with the highest levels of IL-8 had a greater degree of erectile dysfunction., Conclusion: Men with symptomatic benign prostatic hyperplasia and erectile dysfunction had significant inflammation of the prostate to cause spurious rise in PSA level resulting in an unnecessary biopsy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background & Aim: The progression rate of chronic kidney disease (CKD) to its end-stage renal disease (ESRD), and the development and severity of various complications, are indirectly influenced by genetic and epigenetic factors. Chemokines are small inducible pro-inflammatory cytokines, which are implicated in many biological processes like migration of leukocytes, angiogenesis, tumor growth and metastasis. We tested association of four single nucleotide polymorphisms (SNPs) viz. CCL2I/D, CCL2A2518G, CXCL12G801A and CXCR2(+1208)C/T among individuals with ESRD (end stage renal disease) and normal healthy controls from North Indian population., Materials and Method: CCL2I/D, CCL2A2518G, CXCL12G801A and CXCR2(+1208)C/T were genotyped in blood samples of hospital-based case-control study comprising of 200 ESRD cases and 200 healthy controls using Restriction Fragment Length Polymorphism (RFLP) and ARMS (Amplification Refractory Mutation Specific) PCR methodology., Results: A significant association was found in CXCL12G801A with ESRD risk. In case of CXCL12G801A polymorphism heterozygous (GA) genotype showed significant risk (p=0.039; OR=1.55) whereas A allele carrier (GA+AA) also exhibited risk with ESRD (p=0.045, OR=1.59). In CXCR2(+1208)C/T polymorphism, the heterozygous genotype (CT) showed significant risk for ESRD (p=0.028; OR=1.65) and combination of CT+TT demonstrated significant high risk for ESRD (p=0.036; OR=1.52). In case of CCL2I/D, the variant genotype (D/D) showed reduced risk for ESRD patients. Upon analyzing the gene-gene interaction between CXCR2 and CXCL12, the combination (CT-GA) showed 2.65 fold risk for ESRD (p=0.018)., Conclusion: Our results indicated that polymorphism in CXCL12G801A and CXCR2(+1208)C/T showed high risk for ESRD in North Indian population. However, CCL2I/D showed reduced risk and CCL2A2518G exhibited no association. Study with large sample size and diverse ethnicity is required to validate these observations., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: Prostate cancer (CaP) is a heterogeneous, multifactorial, and multifocal disease. Therefore, the search for a combination of functional polymorphisms using cell cycle and apoptotic genes as tumor markers is fundamental for a more precise and reliable diagnosis. In the present study, we investigated the diagnostic value of 3 different genes associated with CaP carcinogenesis, encoding for cell cycle (MDM2, CCND1) and apoptotic (Fas) genes that are differentially expressed in CaP., Methods: In a hospital-based case control study of northern India, blood samples were obtained from 192 CaP patients and 224 cancer-free age matched unrelated healthy controls of similar ethnicity. They were genotyped for MDM2 G309T, CCND1 G870A, Fas A670G, and G1377A polymorphisms using polymerase chain restriction fragment length polymorphism (PCR-RFLP) method., Results: MDM2 309GG variant was at reduced risk for developing CaP (P = 0.041; OR, 0.59). Whereas CCND1 AA genotype demonstrated increased risk (P = 0.018; OR, 1.86). The diplotype analysis of Fas G670A and G1377A (G-A) was observed to be associated with a significant increase in CaP risk (P = 0.024; OR, 1.63)., Conclusion: Findings based on current sample size our results suggested a positive association of CCND1AA genotype and diplotype analysis of Fas G670A and G1377A (G-A) to be associated with CaP risk that could influence the pathophysiology, thereby modulating the risk of CaP., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Polymorphisms in DNA repair genes may be associated with altered DNA repair capacity, thereby influencing an individual's susceptibility to smoking-related cancers such as bladder cancer. Therefore, we sought to examine the correlation between single nucleotide polymorphisms in DNA repair genes and bladder cancer., Methodology: We undertook a case-control study of 212 urothelial bladder cancer (UBC) cases and 250 controls to investigate the association between OGG1 (C1245G rs1052133), XRCC3 (C18067T, rs861539) and XRCC7 (G6721T, rs7003908) polymorphisms and bladder cancer susceptibility by PCR-RFLP and the ARMS method. We also investigated gene-environment interactions., Results: The OGG1 GG genotype was associated with an elevated risk of urothelial bladder cancer (UBC) (OR, 2.10; p, 0.028). XRCC7 + 6721 GG was also associated with increased susceptibility to UBC (OR, 4.45; p, 0.001). In a recessive model, the OGG1 GG genotype showed an increased risk of TaG(2,3) + T1G(1-3) tumors. Additionally, the OGG1 GG genotype in non-smokers represented a 2.46-fold greater risk (OR, 2.46; p, 0.035) in bladder cancer patients. Subsequent analysis demonstrated more pronounced association of XRCC7 with smokers (OR, 4.39; p, 0.001). XRCC7 also showed increased association with TaG(2,3) + T1G(1-3) tumors and muscle invasive tumors (OR, 3.16; p, 0.001 and OR, 4.24; p, 0.001, respectively). Multiple Cox regression analysis in non-muscle invasive bladder tumor (NMIBT) patients demonstrated an association of the OGG1 GG polymorphism with a high risk of recurrence in patients on cystoscopic surveillance (HR, 4.04; p, 0.013). Subsequently, shorter recurrence-free survival (log rank p, 0.024; CC/GG, 42/24) was observed., Conclusion: Our data suggest association of a variant (GG) genotype of OGG1 with increased UBC susceptibility and a high risk of tumor recurrence in NMIBT patients on cystoscopic surveillance. XRCC7 G allele carriers (TG+GG) are also at an elevated risk for susceptibility to UBC as evidenced by a high odds ratio throughout the analysis.

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.

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.

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.