Cystathionine beta-synthase T833C/844INS68 polymorphism: a family-based study on mentally retarded children

• Published in: Behavioral and brain functions Vol. 1; no. 1; p. 25
• Main Authors: Dutta, Samikshan, Sinha, Swagata, Chattopadhyay, Anindita, Gangopadhyay, Prasanta Kumar, Mukhopadhyay, Jotideb, Singh, Manoranjan, Mukhopadhyay, Kanchan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.12.2005; BioMed Central; BMC
• ISSN: 1744-9081; 1744-9081
• DOI: 10.1186/1744-9081-1-25

Cystathionine beta-synthase (CBS) mediates conversion of homocysteine to cystathionine and deficiency in enzyme activity may lead to hyperhomocysteinemia/homocystinuria, which are often associated with mental retardation (MR). A large number of polymorphisms have been reported in the CBS gene, some of which impair its activity and among these, a T833C polymorphism in cis with a 68 bp insertion at 844 in the exon 8 is found to be associated with mild hyperhomocysteinemia in different ethnic groups. The present study is aimed at investigating the association between T833C/844ins68 polymorphism and MR. One hundred and ninety MR cases were recruited after psychometric evaluation. Hundred and thirty-eight control subjects, two hundred and sixty-seven parents of MR probands and thirty cardiovascular disorder (CVD) patients were included for comparison. Peripheral blood was collected after obtaining informed written consent. The T833C/844ins68 polymorphism was investigated by PCR amplification of genomic DNA and restriction fragment length polymorphism analysis, followed by statistical analysis. The genotypic distribution of the polymorphism was within the Hardy-Weinberg equilibrium. A slightly increased genotypic frequency was observed in the Indian control population as compared to other Asian populations. Both haplotype-based haplotype relative risk analysis and transmission disequilibrium test reveled lack of association of the T833C/844ins68 polymorphism with MR; nevertheless, the relative risk calculated was higher (>1) and in a limited number of informative MR families, preferential transmission of the double mutant from heterozygous mothers to the MR probands was noticed (chi2 = 4.00, P < 0.05). This is the first molecular genetic study of CBS gene dealing with T833C/844ins68 double mutation in MR subjects. Our preliminary data indicate lack of association between T833C/844ins68 polymorphism with MR. However, higher relative risk and biased transmission of the double mutation from heterozygous mothers to MR probands are indicative of a risk of association between this polymorphism with mental retardation.