Top

Published in:

01-01-2016 | Original Article

Association Between the 4p16 Susceptibility Locus and the Risk of Atrial Septal Defect in Population from Southeast China

Authors: Kaiyan Pei, Qiuyu Huang, Guican Zhang, Cailing Lu, Benzhang Yu, Liping Yang

Published in: Pediatric Cardiology | Issue 1/2016

Abstract

Three single nucleotide polymorphisms (SNPs), rs16835979, rs870142 and rs6824295, located in chromosome 4p16 were associated with the risk of ostium secundum atrial septal defect (ASD) in the European population. The 4p16 susceptibility locus in congenital heart disease was replicated in Chinese populations. Here, we analyzed the associations between these three SNPs and ASD in Chinese population from Fujian Province in southeast China. We conducted a case–control study by genotyping three SNPs in 354 non-syndromic ASD patients and 557 non-CHD control subjects. Logistic regression analyses showed that the genotype and allele frequencies of these three SNPs were significantly different between the cases and controls in Fujian Chinese population. The allele A of rs870142, the allele A of rs16835979 and the allele A of rs6824295 were significantly associated with an increased risk of ASD. According to the analysis of the three SNPs, the haplotype of AAA was associated with a significantly increased risk of ASD. Our study further supports that these three SNPs confer the predisposition to ASD phenotype in Chinese population.

Basson CT, Bachinsky DR, Lin RC, Levi T, Elkins JA, Soults J, Grayzel D, Kroumpouzou E, Traill TA, Leblanc-Straceski J, Renault B, Kucherlapati R, Seidman JG, Seidman CE (1997) Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt–Oram syndrome. Nat Genet 15:30–35CrossRefPubMed

Boogerd KJ, Wong LY, Christoffels VM, Klarenbeek M, Ruijter JM, Moorman AF, Barnett P (2008) Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43. Cardiovasc Res 78:485–493CrossRefPubMed

Botto LD, Correa A, Erickson JD (2001) Racial and temporal variations in the prevalence of heart defects. Pediatrics 107:E32CrossRefPubMed

Bruneau BG (2008) The developmental genetics of congenital heart disease. Nature 451:943–948CrossRefPubMed

Bruneau BG, Nemer G, Schmitt JP, Charron F, Robitaille L, Caron S, Conner DA, Gessler M, Nemer M, Seidman CE, Seidman JG (2001) A murine model of Holt–Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Cell 106:709–721CrossRefPubMed

Ching YH, Ghosh TK, Cross SJ, Packham EA, Honeyman L, Loughna S, Robinson TE, Dearlove AM, Ribas G, Bonser AJ, Thomas NR, Scotter AJ, Caves LS, Tyrrell GP, Newbury-Ecob RA, Munnich A, Bonnet D, Brook JD (2005) Mutation in myosin heavy chain 6 causes atrial septal defect. Nat Genet 37:423–428CrossRefPubMed

Cordell HJ, Bentham J, Topf A, Zelenika D, Heath S, Mamasoula C, Cosgrove C, Blue G, Granados-Riveron J, Setchfield K, Thornborough C, Breckpot J, Soemedi R, Martin R, Rahman TJ, Hall D, van Engelen K, Moorman AF, Zwinderman AH, Barnett P, Koopmann TT, Adriaens ME, Varro A, George AL Jr, dos Remedios C, Bishopric NH, Bezzina CR, O’Sullivan J, Gewillig M, Bu’Lock FA, Winlaw D, Bhattacharya S, Devriendt K, Brook JD, Mulder BJ, Mital S, Postma AV, Lathrop GM, Farrall M, Goodship JA, Keavney BD (2013) Genome-wide association study of multiple congenital heart disease phenotypes identifies a susceptibility locus for atrial septal defect at chromosome 4p16. Nat Genet 45:822–824PubMedCentralCrossRefPubMed

Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA, Rothrock CR, Eapen RS, Hirayama-Yamada K, Joo K, Matsuoka R, Cohen JC, Srivastava D (2003) GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature 424:443–447CrossRefPubMed

Hu Z, Shi Y, Mo X, Xu J, Zhao B, Lin Y, Yang S, Xu Z, Dai J, Pan S, Da M, Wang X, Qian B, Wen Y, Wen J, Xing J, Guo X, Xia Y, Ma H, Jin G, Yu S, Liu J, Zhou Z, Wang X, Chen Y, Sha J, Shen H (2013) A genome-wide association study identifies two risk loci for congenital heart malformations in Han Chinese populations. Nat Genet 45:818–821CrossRefPubMed

10.

Li QY, Newbury-Ecob RA, Terrett JA, Wilson DI, Curtis AR, Yi CH, Gebuhr T, Bullen PJ, Robson SC, Strachan T, Bonnet D, Lyonnet S, Young ID, Raeburn JA, Buckler AJ, Law DJ, Brook JD (1997) Holt–Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat Genet 15:21–29CrossRefPubMed

11.

Li Z, Zhang Z, He Z, Tang W, Li T, Zeng Z, He L, Shi Y (2009) A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis (http://analysis.bio-x.cn). Cell Res 19:519–523

12.

Olson EN (2006) Gene regulatory networks in the evolution and development of the heart. Science 313:1922–1927PubMedCentralCrossRefPubMed

13.

Posch MG, Perrot A, Berger F, Ozcelik C (2010) Molecular genetics of congenital atrial septal defects. Clin Res Cardiol 99:137–147PubMedCentralCrossRefPubMed

14.

Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, Maron BJ, Seidman CE, Seidman JG (1998) Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 281:108–111CrossRefPubMed

15.

Shi YY, He L (2005) SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res 15:97–98CrossRefPubMed

16.

van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ, Roos-Hesselink JW (2011) Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol 58:2241–2247CrossRefPubMed

17.

Wessels MW, Willems PJ (2010) Genetic factors in non-syndromic congenital heart malformations. Clin Genet 78:103–123CrossRefPubMed

18.

Xie L, Hoffmann AD, Burnicka-Turek O, Friedland-Little JM, Zhang K, Moskowitz IP (2012) Tbx5-hedgehog molecular networks are essential in the second heart field for atrial septation. Dev Cell 23:280–291PubMedCentralCrossRefPubMed

19.

Zhao B, Lin Y, Xu J, Ni B, Da M, Ding C, Hu Y, Zhang K, Yang S, Wang X, Yu S, Chen Y, Mo X, Liu J, Shen H, Sha J, Ma H (2014) Replication of the 4p16 susceptibility locus in congenital heart disease in Han Chinese populations. PLoS One 9:e107411PubMedCentralCrossRefPubMed

20.

Zhao L, Li B, Dian K, Ying B, Lu X, Hu X, An Q, Chen C, Huang C, Tan B, Qin L (2015) Association between the European GWAS-identified susceptibility locus at chromosome 4p16 and the risk of atrial septal defect: a case–control study in Southwest China and a meta-analysis. PLoS One 10:e0123959PubMedCentralCrossRefPubMed

Title: Association Between the 4p16 Susceptibility Locus and the Risk of Atrial Septal Defect in Population from Southeast China
Authors: Kaiyan Pei
Qiuyu Huang
Guican Zhang
Cailing Lu
Benzhang Yu
Liping Yang
Publication date: 01-01-2016
Publisher: Springer US
Published in: Pediatric Cardiology / Issue 1/2016
Print ISSN: 0172-0643
Electronic ISSN: 1432-1971
DOI: https://doi.org/10.1007/s00246-015-1248-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Association Between the 4p16 Susceptibility Locus and the Risk of Atrial Septal Defect in Population from Southeast China

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2016

Safety of Magnetic Resonance Imaging After Implantation of Stainless Steel Embolization Coils

Upcoming Events in Pediatric Cardiology

Decreased Deformation in Asymptomatic Children with Isolated Left Ventricular Non-compaction and Normal Ejection Fraction

IL10 Promoter Polymorphisms are Associated with Rheumatic Heart Disease in Saudi Arabian Patients

Long-Term Prostaglandin E1 Infusion for Newborns with Critical Congenital Heart Disease

Abstracts from the 2nd Annual Fetal Cardiac Symposium Chicago, Illinois, United States September 10–12, 2015