Variations in the inhibin gene in Kashmiri women with primary ovarian insufficiency.

Inhibin is a glycoprotein produced by granulosa cells and its main function is the negative feedback control of follicle stimulating hormone (FSH) which has an important role in folliculogenesis. Mutation in the INHα gene leading to decreased bioactive inhibin has been associated with primary ovarian insufficiency (POI). The aim of this study was to investigate the role of variations in the INHα gene in increasing the susceptibility to POI in Kashmiri women. INHα c.769G > A mutation was analysed in 100 POI cases and 100 controls using PCR-RFLP and agarose gel electrophoresis. The INHα c.769G > A mutation was found in 10% of POI cases with 8% having heterozygous mutation and 2% having a homozygous mutation. The frequency of mutation in healthy controls was zero. Statistically, a very significant association was found between INHα c.769G > A mutation and the occurrence of POI (p = 0.0015). Moreover, the mutation was also significantly associated with high levels of FSH in POI patients (p < 0.0001). Given the significant association of INHα c.769G > A mutation with the increased FSH levels and POI in Kashmiri population, we suggest this mutation can be used to identify POI variants for screening of women susceptible to POI before the disease onset and can further facilitate putative therapy for such patients.

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.

The association between TNFα gene polymorphisms and susceptibility to rheumatoid arthritis in an ethnic Kashmiri population: relationship with disease activity and severity markers.

AIM: The aim of our study was to determine the genetic associations between polymorphisms of the TNFα gene (-308G/A and -238G/A) with disease susceptibility and severity in patients with rheumatoid arthritis (RA) in an ethnic Kashmiri population. METHODS: Allele and genotype frequencies of TNFα-308G/A and TNFα-238G/A polymorphisms were compared between 150 RA patients and 200 healthy controls by using polymerase chain reaction - restriction fragment length polymorphism method. Demographic, clinical and serological data were prospectively evaluated. Disease activity score (DAS28) was also assessed. RESULTS: We did not find any significant association between TNFα-308G/A and TNFα-238G/A polymorphism and RA risk (P > 0.05), but TNFα-308GG genotype was associated significantly with rheumatoid factor seropositivity (P < 0.01) and TNFα-238GA genotype was associated with swollen joint count < 5 (P = 0.04) as well as with less severe disease activity as measured by DAS28 score (P = 0.02). CONCLUSION: Our findings suggest the possible roles of TNFα-308GG and TNFα-238GA as important determinants for the development of certain manifestations and disease severity in RA in ethnic Kashmiri population.

Rheumatoid arthritis and genetic variations in cytokine genes: a population-based study in Kashmir Valley.

OBJECTIVE: The aim of our study was to determine the genetic associations between polymorphisms of the IL1ß gene (-511C/T and +3953C/T) and IL6 gene (-174G/C) with disease susceptibility and severity in patients with rheumatoid arthritis (RA) in ethnic Kashmiri population. METHODS: Allele and genotype frequencies of IL1ß -511 C/T, IL1ß +3953 C/T and IL6 -174 G/C polymorphisms were compared between 150 RA patients and 200 healthy controls by using PCR-RFLP method. RESULTS: We did not find any significant association between IL1b +3953 C/T and IL6 -174 G/C polymorphism and Rheumatoid Arthritis risk (p>0.05), but IL1ß +3953 CT genotype was associated significantly with increased SJC and ESR and IL6 -174 GG genotype was associated significantly with increased ESR. However IL1b -511C/T polymorphism was significantly associated with rheumatoid arthritis risk and the carriers of IL1ß -511 'C' allele (CC and TC genotypes) appeared to have lower risk for RA development. CONCLUSION: Our findings suggest that the IL1b -511 'C' allele has a protective role from disease development. Furthermore our results suggest a possible role of IL1b +3953 CT and IL6 -174 GG genotypes as disease activity markers of rheumatoid arthritis.

Role of vitamin D receptor (VDR) polymorphisms in susceptibility to multiple myeloma in ethnic Kashmiri population.

BACKGROUND: Vitamin D regulates many biological processes including bone metabolism, innate immune response, and cell proliferation and differentiation by binding to its receptor VDR. Vitamin D receptor (VDR) gene polymorphisms have been associated with many cancers like breast, colorectal, prostate, and skin. The main aim of this study was to determine whether VDR polymorphisms (ApaI, BsmI and FokI) are associated with increased risk of multiple myeloma. METHODS: We designed a case control study where 75 multiple myeloma cases were studied for VDR polymorphisms (ApaI, BsmI and FokI) against 150 controls taken from general population. The polymorphisms of VDR gene were investigated using PCR-RFLP method. RESULTS: We did not find any significant association between ApaI and BsmI polymorphisms and multiple myeloma risk (P>0.05), but FokI polymorphism was significantly associated with increased risk for multiple myeloma. We also found a significant association between the ff variant genotype with creatinine levels, albumin levels, and Durie-Salmon stage III. CONCLUSION: Our findings suggest that the FokI polymorphism is involved in the increased susceptibility to development and progression in multiple myeloma in the ethnic Kashmiri population. Furthermore these results suggest that ff genotype is associated with higher risk for developing multiple myeloma.