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J Hum Genet. 2006;51(4):278-283. doi: 10.1007/s10038-005-0356-3. Epub 2006 Feb 18.

MTHFR C677T and A1298C polymorphisms are risk factors for Down's syndrome in Indian mothers.

Author information

1
Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, 221005, Varanasi, India.
2
Department of Zoology, Wolfson College, OX2 6UD, Oxford, UK.
3
Department of Paediatrics, Institute of Medical Sciences, Banaras Hindu University, 221 005, Varanasi, India.
4
Department of Obstetrics and Gynecology, Institute of Medical Sciences, Banaras Hindu University, 221 005, Varanasi, India.
5
Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, 221005, Varanasi, India. rajivaraman@yahoo.com.

Abstract

Down's syndrome (DS), a chromosomal disorder due to trisomy 21, results mostly from nondisjunction in maternal meiosis. The present case-control study examined the association of genetic polymorphisms with predisposition to nondisjunction. Two common polymorphisms (SNPs), C677T and A1298C, in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene involved in folate metabolism, are known to lower the activity of this enzyme. Three hundred and fourteen mothers (with DS children and controls), mostly from the eastern states of India, were genotyped for the two above-mentioned SNPs. Significant association with both of these SNPs were detected, more specifically, in the mothers of DS children homozygous for the polymorphic alleles 677 T and 1298 C. The relative risk of T (C677T) and C (A1298C) homozygosity in mothers for DS-affected pregnancy was 7 (OR 7.67, 95% CI 1.67-35.08, P=0.003) and 4 (OR 4.40, 95% CI 1.45-13.26, P=0.008), respectively. Moreover, all 677TT mothers studied were less than 31 years of age, whereas no correlation with maternal age was observed for A1298C genotypes. Interestingly, all of the young 677TT mothers had either a first- or secondborn child with DS. Thus, this study reports that young Indian mothers with TT genotypes are genetically predisposed to nondisjunction due to abnormal folate metabolism.

PMID:
16489479
DOI:
10.1007/s10038-005-0356-3
[Indexed for MEDLINE]

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