Publication: Folate System Gene Variant rs1801394 66A>G may have a Causal Role in Down Syndrome in the Eastern Indian Population
Issued Date
2020-01-01
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ISSN
22519645
22519637
22519637
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2-s2.0-85098884092
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Mahidol University
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SCOPUS
Bibliographic Citation
International Journal of Molecular and Cellular Medicine. Vol.9, No.3 (2020), 215-223
Suggested Citation
Mahasweta Chatterjee, Tanusree Saha, Subhamita Maitra, Swagata Sinha, Kanchan Mukhopadhyay Folate System Gene Variant rs1801394 66A>G may have a Causal Role in Down Syndrome in the Eastern Indian Population. International Journal of Molecular and Cellular Medicine. Vol.9, No.3 (2020), 215-223. doi:10.22088/IJMCM.BUMS.9.3.215 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/60883
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Title
Folate System Gene Variant rs1801394 66A>G may have a Causal Role in Down Syndrome in the Eastern Indian Population
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Abstract
© 2020 All Rights Reserved Down syndrome (DS) is associated with trisomy of the 21st chromosome in more than 95% cases. The extra chromosome mostly derives due to abnormal chromosomal segregation, i.e. non-disjunction, during meiosis. Earlier reports showed that abnormal folate metabolism can lead to DNA hypomethylation and abnormal chromosomal segregation. We analyzed three functional folate gene variants, namely 5-methyltetrahydrofolatehomocysteine methyltransferase rs1805087, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase rs1801394, and reduced folate carrier 1 rs1051266, for contribution in the etiology of DS. Ethnically matched subjects including DS probands (N=183), their parents (N=273), and controls (N=286) were recruited after obtaining informed written consent for participation. Karyotype analysis confirmed trisomy 21 in DS patients recruited. Genomic DNA, purified from peripheral blood leukocytes was used for genotyping of the target sites by PCR based methods, and data obtained was subjected to population- as well as family-based association analysis. Frequency of rs1801394 ‘G’ allele and ‘GG’ genotype was higher in DS probands (P < 0.0001). Statistically significant higher occurrence of the ‘G’ allele in parents of DS probands (P < 0.0001) and maternal bias in transmission of the “G” allele was also noticed (P < 0.0001). Genetic model analysis demonstrated rs1801394 “G” as a risk allele under both dominant and recessive models. DS probands also showed higher occurrence of rs1051266 “G” (P = 0.05). Quantitative trait analysis revealed significant negative influence of rs1805087 “A” on birth weight. Screening for rs1801394 “G” could be useful in monitoring the risk of DS, at least in the studied population.
