Replication analysis of 15 susceptibility loci for nonsyndromic cleft lip with or without cleft palate in an italian population.

Autor: Cura F; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy., Böhmer AC; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Klamt J; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Schünke H; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Scapoli L; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy., Martinelli M; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy., Carinci F; Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy., Nöthen MM; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Knapp M; Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany., Ludwig KU; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany., Mangold E; Institute of Human Genetics, University of Bonn, Bonn, Germany.
Jazyk: angličtina
Zdroj: Birth defects research. Part A, Clinical and molecular teratology [Birth Defects Res A Clin Mol Teratol] 2016 Feb; Vol. 106 (2), pp. 81-7. Date of Electronic Publication: 2015 Dec 09.
DOI: 10.1002/bdra.23454
Abstrakt: Background: Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common congenital malformations in humans. Its average global incidence is 1.7 per 1000 live births, with wide variation according to geographical location and ethnicity. Its etiology involves both genetic and environmental factors. The aim of the present study was to confirm genetic association of a selection of 15 candidate nsCL/P loci using an independent sample of the Italian population.
Methods: At least one single-nucleotide polymorphism (SNP) for each locus was genotyped in 380 nuclear trios.
Results: Transmission disequilibrium analysis revealed significant associations for three variants at two loci (8q24 and 1p22). Two SNPs at 8q24 showed the strongest level of association, the rs987525 (PTDT  = 6.81 × 10(-6) ; homozygous relative risk = 3.60 [95% confidence interval, 2.12-6.13]), and the rs17241253 (PTDT  = 1.03 × 10(-5) ; homozygous relative risk = 3.75 [95% confidence interval, 2.10-6.67]). Four additional loci (at 1q32, 3q12, 8q21, and 10q25) achieved nominally significant p-values. Two SNPs at 1p36 achieved p-values of < 0.1. The present data suggest that 6 of the 15 analyzed nsCL/P risk loci contribute significantly to nsCL/P risk in the Italian population. These include the 1p22 locus, which previous research has implicated predominantly in Asian populations.
Conclusion: Different loci, including 8q24 and 1p22 have been found associated with nsCL/P in multiple populations. Further efforts are needed to identify causative variants and transfer knowledge to clinical application, such as personal genetic risk assessment.
(© 2015 Wiley Periodicals, Inc.)
Databáze: MEDLINE
Externí odkaz: