International Journal of Molecular and Cellular Medicine
مجله بین المللی سلولی و مولکولی
Int J Mol Cell Med
Medical Sciences
http://ijmcmed.org
1
admin
2251-9637
2251-9645
10.22088/IJMCM.BUMS
en
jalali
1399
5
1
gregorian
2020
8
1
9
3
online
1
fulltext
en
Folate System Gene Variant rs1801394 66A>G may have a Causal Role in Down Syndrome in the Eastern Indian Population
Genetics & Disease
Genetics & Disease
Original Article
Original Article
Down syndrome (DS) is associated with trisomy of the 21<sup>st</sup> 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-methyltetrahydrofolate-homocysteine 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.
Down syndrome, DNA hypomethylation, folate, rs1805087, rs1801394, rs1051266
215
223
http://ijmcmed.org/browse.php?a_code=A-10-2390-1&slc_lang=en&sid=1
Mahasweta
Chatterjee
mahaswetachatterjee1991@gmail.com
100319475328460018968
100319475328460018968
No
Manovikas Biomedical Research and Diagnostic Centre, MRIH, Kolkata, India.
Tanusree
Saha
tanusreesaha_microbio@yahoo.in
100319475328460018969
100319475328460018969
No
Manovikas Biomedical Research and Diagnostic Centre, MRIH, Kolkata, India.
Subhamita
Maitra
msubhamita4u@yahoo.com
100319475328460018970
100319475328460018970
No
Manovikas Biomedical Research and Diagnostic Centre, MRIH, Kolkata, India.
Swagata
Sinha
swagata7sinha@hotmail.com
100319475328460018971
100319475328460018971
No
Manovikas Biomedical Research and Diagnostic Centre, MRIH, Kolkata, India.
Kanchan
Mukhopadhyay
drkanchanm@gmail.com
100319475328460018972
100319475328460018972
Yes
Manovikas Biomedical Research and Diagnostic Centre, MRIH, Kolkata, India.