How to Cite this Article: Ghosh P, Bhaumik P, Ghosh S, Ozbek U, Feingold E, Maslen C, Sarkar B, Pramanik V, Biswas P, Bandyopadhyay B, Dey SK. 2012. Polymorphic haplotypes of CRELD1 differentially predispose Down syndrome and euploids individuals to atrioventricular septal defect. Am J Med Genet Part A 158A: 2843–2848.
Polymorphic haplotypes of CRELD1 differentially predispose Down syndrome and euploids individuals to atrioventricular septal defect†
Version of Record online: 14 SEP 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Special Issue: SPECIAL ISSUE: GROWTH CHARTS IN GENETIC SYNDROMES
Volume 158A, Issue 11, pages 2843–2848, November 2012
How to Cite
Ghosh, P., Bhaumik, P., Ghosh, S., Ozbek, U., Feingold, E., Maslen, C., Sarkar, B., Pramanik, V., Biswas, P., Bandyopadhyay, B. and Dey, S. K. (2012), Polymorphic haplotypes of CRELD1 differentially predispose Down syndrome and euploids individuals to atrioventricular septal defect. Am. J. Med. Genet., 158A: 2843–2848. doi: 10.1002/ajmg.a.35626
- Issue online: 17 OCT 2012
- Version of Record online: 14 SEP 2012
- Manuscript Accepted: 26 JUL 2012
- Manuscript Received: 17 FEB 2012
- Council of Scientific and Industrial Research (CSIR), New Delhi, India. Grant Number: 27(0225)/10/EMRII
- Down syndrome;
- atrioventricular septal defect;
- single nucleotide polymorphism;
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. © 2012 Wiley Periodicals, Inc.