Recent evidence indicates the involvement of microRNAs (miRNAs), in cell growth control, differentiation, and apoptosis, thus playing a role in tumorigenesis. Single-nucleotide polymorphisms (SNPs) located at miRNA-binding sites (miRNA-binding SNPs) are likely to affect the expression of the miRNA target and may contribute to the susceptibility of humans to common diseases. We genotyped SNPs hsa-mir196a2 (rs11614913), hsa-mir146a (rs2910164), and hsa-mir499 (rs3746444) in a case-control study including 159 prostate cancer patients and 230 matched controls. Patients with heterozygous genotype in hsa-mir196a2 and hsa-mir499, showed significant risk for developing prostate cancer (P = 0.01; OR = 1.70 and P ≤ 0.001; OR = 2.27, respectively). Similarly, the variant allele carrier was also associated with prostate cancer, (P = 0.01; OR = 1.66 and P ≤ 0.001; OR = 1.97, respectively) whereas, hsa-mir146a revealed no association in prostate cancer. None of the miRNA polymorphisms were associated with Gleason grade and bone metastasis. This is the first study on Indian population substantially presenting that individual as well as combined genotypes of miRNA-related variants may be used to predict the risk of prostate cancer and may be useful for identifying patients at high risk.

MicroRNAs (miRNA) are a class of small noncoding RNA molecules that have been implicated in a wide variety of cellular functions through post-transcriptional regulations on target genes. Common genetic variants (single-nucleotide polymorphisms, SNPs) in pre-miRNA genes may alter their expression and/or maturation effecting thousands of target mRNAs, resulting in varied functional consequences. Three common SNPs (hsa-mir-146a G>C rs2910164, hsa-mir-196a2 C>T rs11614913, and hsa-mir-499 T>C rs3746444) in pre-miRNAs were investigated to evaluate their association with urinary bladder cancer risk. The hospital-based case-control study comprised of 212 histologically confirmed patients with urinary bladder cancer and 250 healthy controls who were unrelated, of similar ethnicity, and age and gender matched. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism methodology. Our results showed that the heterozygous genotype of rs11614913 was higher in cases than controls but the results were marginally significant (p = 0.055; odds ratio, 1.44). Smoking had no impact in modulating the effect of any of the three miRNA SNPs studied. No association was observed with either the tumor stage or grade in patients with bladder cancer. Even though there was no association between the individuals carrying the variant genotypes of the three miRNA studied and bladder cancer risk, marginal significance of heterozygousity in rs11614913 suggested further characterization of miRNA SNPs in a large cohort of varied ethnicity. This could further provide new prospects for understanding the underlying mechanisms between miRNAs and disease etiology.

Prostate cancer (PCa) is the most common cancer among men. It has been suggested that toll like receptors (TLRs) may contribute to PCa pathogenesis by stimulating prostate epithelial cell proliferation in response to infectious stimuli. We performed case control study to analyze the genetic variants of TLR2, 3 and 9 gene polymorphisms with PCa risk in a North Indian population. For this study we genotyped age matched, unrelated 195 PCa patients and 250 healthy controls of similar ethnicity in a case-control study. They were genotyped for TLR2 (-196 to -174 Del), TLR3 (c.1377C/T) [rs3775290] and TLR9 (G2848A) [rs352140] gene polymorphisms using polymerase chain reaction and restriction fragment length polymorphism method. Variant allele Del (D) carriers i.e. (ID + DD) of TLR2 (-196 to -174 Del) SNP, demonstrated 1.57 fold increased risk (p = 0.040; OR = 1.57, 95% CI = 1.02-2.24) as compared to Ins (I) allele, suggesting a dominant effect model involved in the risk of this polymorphism in PCa. However, variants of TLR3 and 9 gene polymorphisms were not associated with PCa risk. Our results suggested the low penetrance variant of TLR2 (-196 to -174 Del) to be at increased PCa risk in North Indian population. Functional studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in identifying the disease-associated variants for PCa etiology.

No abstract

No abstract

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator (AIRE) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1-7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.

No abstract

No abstract