Interleukin 32 gene promoter polymorphism: A genetic risk factor for multiple sclerosis in Kashmiri population.

OBJECTIVE: Although the exact cause of multiple sclerosis is not known, there are a number of factors involved mainly environmental and genetic factors. The present study was done to determine association between IL-32 gene promoter polymorphism and IL-32 levels with multiple sclerosis. METHODS: 48 relapsing remitting multiple sclerosis patients and 60 healthy controls were compared for IL-32 gene promoter polymorphism and IL-32 levels. RESULTS: There was no significant difference in genotype CT between the MS patients and healthy controls (p 0.130) where as a significant difference in genotype (CC) frequencies among MS patients and healthy controls (p 0.039) was observed. The difference in C allele frequency was also statistically significant between two study groups (p 0.01). Multivariate regression analysis revealed that the CC genotype might impact the risk of disease susceptibility up to 3.71 times and the presence of C allele might increase the risk of susceptibility to multiple sclerosis by 2.26 fold. The serum IL-32 levels were not statistically different multiple sclerosis patients and healthy controls and between wild and mutant genotypes. CONCLUSIONS: IL-32 gene promoter polymorphism is a genetic risk factor for multiple sclerosis patients particularly women.

High incidences of chromosomal aberrations and Y chromosome micro-deletions as prominent causes for recurrent pregnancy losses in highly ethnic and consanguineous population.

PURPOSE: Recurrent Miscarriages (RM) commonly complicates the reproductive outcome where prominently chromosomal aberrations and molecular factors lead to recurrent miscarriages. We investigated couples with RM for cytogenetic abnormalities and Y chromosome microdeletions in males along with detection of aneuploidies de novo in the product of conception from a highly ethnic consanguineous population (Kashmir, North India) . STUDY DESIGN: Chromosomal analysis was done by Karyotyping on peripheral blood lymphocyte cultures and analyzed by Cytovision software Version 3.9. Microdeletion in Y chromosome was performed by STS-PCR and QF-PCR was used to detect aneuploidy in the product of conception. RESULTS: Of the 380 samples (190 couples) screened for cytogenetic analysis, 50 (13.1%) chromosomal aberrations were detected in both couples. Numerical aberrations were detected in 16.0%, inversions 22%, duplications 16.0% and translocations were found in 26.0% with three unique reciprocal translocations in males. The couples bonded consanguineously had 32% chromosomal changes with a significant difference in chromosomal inversions (37.5% vs. 14.7%) and translocations (37.5% vs. 20.6%) for consanguineous and non-consanguineous group, respectively (p < 0.05). Further, translocations and inversions (44.5% and 33.3%) were significantly implicated in couples with a positive family history of RM (p < 0.05). Y chromosome deletions were found in 2.1% cases of males. CONCLUSION: We conclude 15.2% couples affected either by chromosomal or Y chromosome deletions contribute hugely in the diagnosis and management of repeated pregnancy losses. It is recommended that couples that belong to consanguineous and multigenerational group of RM should be considered for cytogenetic and molecular testing after two abortions for successful pregnancy outcomes and management of RM.

High prevalence of factor V Leiden and prothrombin G20101A mutations in Kashmiri patients with venous thromboembolism.

AIM: The genetic variants of the factor V (G1691A), prothrombin (G20210A) and MTHFR (C677T) genes have been widely implicated as inherited risk factors for developing venous thrombosis. This study was undertaken to reveal the frequency of these mutations in Kashmiri patients with venous thromboembolism. METHODOLOGY: A case-control study was designed with 250 VTE patients and 250 healthy controls. The mutations were analysed using ARMS-PCR and PCR-RFLP approach. RESULT: The factor V Leiden G1691A mutation was found in 17/250 (6.8%) VTE patients and prothrombin G20210A mutation was found in 7/250 (2.8%) VTE patients while no mutation was found in any of the healthy controls. Both the mutations were found to be significantly associated with the increased risk of VTE (p = 0.0001 and 0.0150 respectively) while no association of VTE risk with MTHFR C677T polymorphism was found (p = 0.53). CONCLUSION: The increased frequency of factor V Leiden G1691A and prothrombin G20210A mutation in VTE patients indicates a significant role of these mutations in the development of VTE in our population. We therefore suggest the routine screening of these two mutations as thrombophilic markers in Kashmiri patients with venous thromboembolism.