Niyaz A. Naykoo

Lack of Association of a Common Polymorphism in the 3`-UTR of Interleukin 8 with Non Small Cell Lung Cancer in Kashmir

BACKGROUND Chronic inflammation is considered as an important factor in the pathogenesis of lung cancer. The presence of inflammatory cells and higher levels of pro-inflammatory cytokines in the tumor microenvironment and their surrounding tissues is gaining much importance in research. MATERIALS AND METHODS One hundred ninety NSCLC cases and 200 age, smoking and sex matched controls were evaluated for association of IL-8 -251 (rs4073) and IL-8 -845 (rs2227532) in our population. Restriction fragment length polymorphism (RFLP) was used followed by direct sequencing for the detection of SNPs. RESULTS The IL-8 -845 polymorphism was not found in our population. No significant association was observed between the IL-8 -251 AT genotypes and IL-8 -25 AA genotypes and NSCLC (p=0.05) in our population. The IL-8 -251 A allele was also non-significant (p=0.05) in NSCLC patients. CONCLUSIONS In conclusion, this report reveals lack of association between IL-8 - 251 A/T polymorphism and NSCLC in our Kashmir Valley population.

WITHDRAWN: Single nucleotide polymorphisms, haplotype association and tumour expression of the vascular endothelial growth factor (VEGF) gene with lung carcinoma.

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Trp homozygotes at codon 64 of ADRB3 gene are protected against the risk of type 2 diabetes in the Kashmiri population.

The prevalence of type 2 diabetes mellitus has reached epidemic proportions worldwide. Type 2 diabetes is a consequence of complex interactions among multiple genetic variants and environmental risk factors. Polymorphisms in various candidate genes confer susceptibility to diabetes. This study was undertaken to analyse a single nucleotide polymorphism Trp64Arg (C↔T) in the ADRB3 gene and elucidate its effects on type 2 diabetes and its associated risk factors. The study included 200 type 2 diabetes patients and 300 age and gender matched healthy controls belonging to the ethnic Kashmiri population. Polymerase chain reaction-restriction fragment length polymorphism technique was used for genotyping and the results were validated by direct sequencing assay. Genotypes for Trp64Arg polymorphism were in Hardy-Weinberg equilibrium (χ(2)=0.48, p=NS). Frequency of the Arg64 allele was 40% and 10.2% in cases and controls, respectively (p<0.05; odds ratio 5.89; 95% CI; 3.69-9.39). The Arg64 allele was directly related to higher body mass index, waist-to-hip ratio, dyslipidemia and uncontrolled disease status. The study signifies that the Arg64 allele of the ADRB3 gene is a genotypic risk factor and confers susceptibility to type 2 diabetes, whereas the homozygous Trp64 genotype exerted a protective effect in our population.

Possible Impact of RET Polymorphism and Its Haplotypic Association Modulates the Susceptibility to Thyroid Cancer

Rearranged during Transfection (RET) gene polymorphisms act to influence thyroid cancer in a polygenic and low‐penetrance manner and no study regarding RET alterations in thyroid cancer has undergone from this part of the world (North India). We evaluated RET G691S (rs1799939), L769L (rs1800861), and S904S (rs1800863) polymorphisms to elucidate their possible role as risk factors in papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Polymorphic analysis of RET gene was performed by polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP). In RET G691S polymorphism, the overall distribution of variant alleles (GA + AA) in cases was 62.9% as against 44.5% in controls (P < 0.05) whereas frequency of RET L769L variant alleles (TG + GG) in cases was 70% versus 88% in controls (P < 0.05). In RET S904S, frequency of variant alleles (CG + GG) in cases was 56% versus 44% in controls (P < 0.05). Interestingly, G691S/L769L variant showed increased risk for the non‐smokers (P < 0.05). RET S904S variant showed association with benign thyroid disease as against those with no history. The over‐representation of homozygotes in G691S and L769L polymorphic variants was not observed, which suggest a “Dominant mode of inheritance.” The S904S polymorphism heterozygote lies almost in the middle of the two homozygotes confirming an “Additive mode of inheritance.” In conclusion, RET gene G691S/S904S polymorphisms were over‐represented and L769L polymorphism was under‐represented in PTC and FTC patients. RET polymorphic variants could act synergistically in the development or progression of PTC and FTC. J. Cell. Biochem. 116: 1712–1718, 2015.

TGIF1 is a Potential Candidate Gene for High Myopia in Ethnic Kashmiri Population

Abstract Purpose: High myopia is a complex disorder that imposes serious consequences on ocular health. Linkage analysis has identified several genetic loci with a series of potential candidate genes that reveal an ambiguous pattern of association with high myopia due to population heterogeneity. We have accordingly chosen to examine the prospect of association of one such gene [transforming growth β-induced factor 1 (TGIF1)] in population that is purely ethnic (Kashmiri) and represents a homogeneous cohort from Northern India. Methods: Cases with high myopia with a spherical equivalent of ≥−6 diopters (D) and emmetropic controls with spherical equivalent within ±0.5 D in one or both eyes represented by a sample size of 212 ethnic Kashmiri subjects and 239 matched controls. Genomic DNA was genotyped for sequence variations in TGIF1 gene and allele frequencies tested for Hardy–Weinberg disequilibrium. Potential association was evaluated using χ2 or Fisher’s exact test. Results: Two previously reported missense variations C > T, rs4468717 (first base of codon 143) changing proline to serine and rs2229333 (second base of codon 143) changing proline to leucine were identified in exon 10 of TGIF1. Both variations exhibited possibly significant (p < 0.05) association with the disease phenotype. Since the variant allele frequency of both the single-nucleotide polymorphisms in cases is higher than controls with odds ratio greater than 1.Therefore, variant allele of both the single-nucleotide polymorphisms represents the possible risk factor for myopia in the Kashmiri population. In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia. Conclusions: TGIF1 is a relevant candidate gene with potential to contribute in the genesis of high myopia.