SEMA3A rs7804122 polymorphism is associated with Hirschsprung disease in the Northeastern region of China

Authors

  • Li–Li Wang,

    1. Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, People's Republic of China
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  • Yi Zhang,

    1. Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, People's Republic of China
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  • Yang Fan,

    1. Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, People's Republic of China
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  • Hui Li,

    1. Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, People's Republic of China
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  • Feng–hua Zhou,

    1. Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, People's Republic of China
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  • Jia-Ning Miao,

    1. Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, People's Republic of China
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  • Hui Gu,

    1. Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, People's Republic of China
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  • Tian–Chu Huang,

    1. Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, People's Republic of China
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  • Zheng–Wei Yuan

    Corresponding author
    1. Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004, People's Republic of China
    • No. 36, Sanhao Street, Heping District, Shenyang, China, 110004, Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, 110004 P.R. China
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  • Funding for this study was supported by a grant from the National Natural Science Foundation of China (30872705, 81100434), Specialized Research Fund for the Doctoral Program of Higher Education (20102104120014, 20092104120010), and Scientific Research Fund of Liaoning Provincial Education Department (L2010637).

  • Competing interests statement: The authors have no competing interests to declare.

Abstract

BACKGROUND

Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of intrinsic ganglion cells in the nerve plexuses of the lower colon. Our previous results showed increased semaphorin 3A (SEMA3A) expression may be the risk factor for HSCR pathology in a subset of patients. Therefore, the association between polymorphisms in SEMA3A and the risk of HSCR was examined.

METHODS

The genotypes of two SNPs (rs7804122 and rs797821) in the SEMA3A gene in 119 patients with HSCR and 93 controls were examined using PCR-sequencing to determine the contribution of SEMA3A to the HSCR phenotype. PCR reaction with cDNA template was also used to find out whether a novel mutation (Chr7:83634610A→T) influences the SEMA3A pre-mRNA splicing.

RESULTS

Genotypes comprising allele G of rs7804122 (GG or AG) were over-represented in patients (48.74 vs. 24.8%; p = 0.0013) which indicated that the risk of HSCR was significantly higher among subjects with the GG or AG genotype than among the subjects with the AA genotype. No statistically significant associations were found for SNP rs797821 at the allele or genotype levels. The differences in genotypes and allele distributions of rs7804122 and rs797821 between various clinical classifications were not statistically significant. The novel heterozygous mutation (Chr7:83634610A→T) 30bp away from an intron/exon boundary, had no detectable effect on splicing efficiency.

CONCLUSION

Our results for rs7804122 provided preliminary evidence that the SEMA3A gene is involved in the susceptibility to HSCR in the Northeastern Chinese population. Birth Defects Research (Part A) 2012. © 2011 Wiley Periodicals, Inc.

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