Role of APOE and IL18RAP gene polymorphisms in cervical spondylotic myelopathy in Indian population.

Cervical spondylotic myelopathy (CSM) is a progressive degenerative spine disease. It is not clear why certain patients develop symptomatic myelopathy whereas others do not, even in the presence of radiographic features of cervical stenosis. Genetic predisposition has been suggested, supported by familial occurrence of CSM. In this study we explored the demographic and radiographic features of CSM in Indian population and studied the association between polymorphisms in interleukin18RAP and apo-lipoprotein genes in CSM. A total of 100 CSM patients and 100 healthy control subjects were included in this study. Genotyping of APOE (rs7412 and rs429358) and IL18RAP (rs1420106 and rs917997) gene polymorphisms was performed by Taqman allelic discrimination assay. Comparison of allelic frequencies, ε2 versus ε3 (OR = 4.4, 95%CI = 1.23-15.73, P = 0.002) and ε2 versus ε4 (OR = 6.67, 95%CI = 1.58-28.04, P = 0.009) showed a statistically significant association for the risk of CSM. There was no significant association between different genotypes with sex, T2 signal intensity change and Nurick grade. Only patients having multiple level cervical prolapsed intervertebral disc (PIVD) on MRI, had a higher proportion of the ε2 allele as compared to controls (p = <0.0001). No significant association was found between IL18RAP gene polymorphisms (rs1420106 and rs917997) with the risk of CSM. ε2 allele was associated with the risk of CSM in Indian population. There was no significant association between the two single nucleotide polymorphisms (SNPs) of IL18RAP gene with risk of CSM.

Effect of rs11614913 Polymorphism on Mature miR196a2 Expression and its Target Gene HOXC8 Expression in Human Glioma.

miRNA polymorphisms are recently identified as a risk factor for various cancers, and it is associated with change in the expression of target genes in vitro. rs11614913 polymorphism in miR196a2 was associated with risk of glioma in Chinese population. In this study, we have evaluated the role of rs11614913 polymorphism and glioma risk in Indian population in 180 cases and controls. Seventy-two glioma tissue-blood pairs were also assessed for mutation in this SNP. Further, the effect of this polymorphism on mature miR196a2 expression and HOXC8 gene expression was analysed in 33 glioma tissue samples with different genotypes. Allelic discrimination assay was performed for genotyping and quantitative real time PCR for the expression of miR196a2 and HOXC8 gene. We could not find any association between rs11614913 polymorphism and glioma risk in Indian population. The rs11614913 genotyping of glioma tissue and blood pair revealed presence of mutations showing changes from C to T allele in majority of samples. The expression of the mature miR196a2 was significantly high in glioma samples, but there was no difference in expression with genotype. HOXC8 gene expression was not significantly different in glioma tissue when compared to non-glioma and interestingly there was a significant difference in expression with different genotypes, especially TT genotype was showing over expression when compared to other genotypes. Our study suggests that the rs11614913 polymorphism does not affect the mature miRNA expression, but shows its effect through target gene HOXC8 expression in glioma.

Two gene polymorphisms (rs4977756 and rs11515) in CDKN2A/B and glioma risk in South Indian population.

Gliomas are most common neoplasms in the CNS with unknown aetiology. Gene polymorphisms have been studied in glioma to check its risk in different population. CDKN2A, commonly altered tumor suppressor gene polymorphisms were recently shown to be associated with glioma in Caucasians. Present study evaluated potential association between two SNPs in CDKN2A/B gene with glioma risk in South Indian population with a total of 128 cases and 140 control subjects. Allelic discrimination assay was used for the genotyping and the association of each SNP with glioma risk were calculated using odds ratio and 95% CI. There was no association between rs4977756 polymorphism and glioma risk in south Indian population. GG genotype had a non-significant low risk in glioma (OR = 0.69). rs11515 polymorphism was not in Hardy Weinberg Equilibrium in our sample, so it was not considered for association studies. There was difference in genotype in tissue samples paired with blood samples for rs4977756 polymorphism, suggesting the importance of tissue SNP status in association studies. These results show that these two polymorphisms may not contribute to risk for glioma in South Indian population.