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Komaravalli, Prasanna Latha and Vasantha Rani, S. and Dalal, Ashwin and Jahan, Parveen (2020) Association analysis of FMR1 genetic variants and Primary Ovarian Insufficiency in South Indian women with a novel approach of CGG repeats classification. European Journal of Medical Genetics, 63 (12). p. 104081. ISSN 1769-7212

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Abstract

Around 20-28% of FMR1gene CGG premutation (PM) carriers are at augmented risk towards an infertility related disorder, Fragile X-associated primary ovarian insufficiency (FXPOI). Except the effect of CGG repeats, reports are not available on the mechanism through which the cis-acting variations, namely, SNPs involved in POI susceptibility. Addressing the hypothesis that the FMR1 gene polymorphisms [CGG repeats, rs25731(T>A) and rs4949(A>G)] might increase their individual and combined impact in disease predisposition, we tested the genetic variants in 200 south Indian DNA samples consists of 100 patients and 100 healthy volunteers. We used gene scan method to score the CGG repeat length, and ARMS and RFLP methods to genotype the SNPs. Only 0.5% of each Gray zone and PM alleles were found among patient group, however, no disease association was noticed with repeat length. The rs25731 showed protection [OR:0.32;(0.13-0.76),p=0.006] and rs4949 reported a 2.5-fold risk towards the disease predisposition [OR:2.46;(1.06-5.74),p=0.031] but, both found insignificant after Bonferroni correction was done under different Genetic Models. Novel classification of genotype combinations, 'Normal&Variant Homozygote' [OR:2.89,(1.12- 7.9),p<0.05] and 'Allele2-T-G' haplotype block (6%vs.1%,p=0.08) were noticed to be at marginal risk for POI. We demonstrated a susceptible role of the combined effect of variant allele-G and Allele-2 (repeat allele outside the normal range) for FXPOI. To support our findings of its first kind, further studies with large samples are warranted in understanding the role of FMR1 genetic variants in FXPOI etio-pathophysiology, the outcome might help in providing better reproductive treatment options for females, who are at risk for FXPOI.

Item Type: Article
Subjects: Genetics
Depositing User: Dr P. Divakar
Date Deposited: 18 Oct 2020 12:32
Last Modified: 10 Nov 2020 18:34
URI: http://cdfd.sciencecentral.in/id/eprint/977

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