Polymorphic haplotypes of CRELD1 differentially predispose Down syndrome and euploids individuals to atrioventricular septal defect

Priyanka Ghosh, Pranami Bhaumik, Sujoy Ghosh, Umut Ozbek, Eleanor Feingold, Cheryl Maslen, Biswanath Sarkar, Vishmadeb Pramanik, Priyanka Biswas, Biswajit Bandyopadhyay, Subrata Kumar Dey

    Research output: Contribution to journalArticle

    5 Scopus citations

    Abstract

    To explore the role of CRELD1 variants on congenital heart defects, we sequenced the entire reading frame of CRELD1 in the samples from Kolkata and adjoining areas. Nearly, 400 participants were included in the genetic association study and they were stratified as Down syndrome (DS) with atrioventricular septal defect (AVSD), DS without AVSD, euploid with AVSD, and euploid without AVSD. A significant association was found between AVSD and three polymorphisms, namely rs9878047 (c.1049-129T>C), rs3774207 (c.1119C>T), and rs73118372 (c.1136T>C) among the Down syndrome and euploid individuals. The polymorphism rs73118372, involves a transition (c.1136T>C) that leads to change in amino acid methionine to threonine which alters protein secondary structure as confirmed by the bioinformatics software SOPMA. In addition, two haplotypes, C-T-C and C-T-T, in the order of loci rs9878047-rs3774207-rs73118372 were associated with incidence of AVSD among euploid and Down syndrome, with a slightly higher odds ratio in the later group. We hypothesize that these haplotypes increase the risk of AVSD, and the susceptibility is exacerbated in DS, possibly due to the trisomy 21 genetic background. Moreover, we report for the first time on an interaction between the mutant alleles of rs3774207 and rs73118372 which could disrupt the delicate balance between different CRELD1 isoforms.

    Original languageEnglish (US)
    Pages (from-to)2843-2848
    Number of pages6
    JournalAmerican Journal of Medical Genetics, Part A
    Volume158 A
    Issue number11
    DOIs
    StatePublished - Nov 2012

    Keywords

    • Atrioventricular septal defect
    • CRELD1
    • Down syndrome
    • Single nucleotide polymorphism
    • Splicing

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

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  • Cite this

    Ghosh, P., Bhaumik, P., Ghosh, S., Ozbek, U., Feingold, E., Maslen, C., Sarkar, B., Pramanik, V., Biswas, P., Bandyopadhyay, B., & Dey, S. K. (2012). Polymorphic haplotypes of CRELD1 differentially predispose Down syndrome and euploids individuals to atrioventricular septal defect. American Journal of Medical Genetics, Part A, 158 A(11), 2843-2848. https://doi.org/10.1002/ajmg.a.35626