Abstract
Purpose
Recently, genetic markers within a locus on 7q21.11 containing the SEMA3A, SEMA3C, and SEMA3D genes were reported to be associated with Hirschsprung disease (HSCR). Here, we investigated three polymorphisms, rs1583147, rs12707682, and rs11766001, at this locus to determine their potential contributions to the susceptibility of Indonesian HSCR patients.
Methods
Three variants were analyzed in 60 non-syndromic HSCR patients and 118 ethnicity-matched controls for association studies by genotyping.
Results
The risk allele frequencies of SEMA3 rs12707682 (allele C) and rs1583147 (allele T) is higher in cases, 53 and 23 %, than in controls, at 42 and 13 %, respectively. However, these frequency differences were not statistically significant with p value of 0.06 and 0.023, respectively. These findings were consistent with transmission disequilibrium test results with p values of 0.041 and 0.11 for rs12707682 and rs1583147, respectively. Furthermore, the frequencies of SEMA3 rs11766001 risk allele in HSCR cases and controls were 1.7 and 0.8 %, respectively.
Conclusions
SEMA3 rs12707682 and rs1583147 variants are not common risk factors for HSCR in Indonesia. The rarity of the SEMA3 rs11766001 polymorphism in Indonesian population might be due to a founder effect.
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Acknowledgments
We thank the patients and their families who have contributed in these studies. We also thank Prof. Aravinda Chakravarti (Johns Hopkins University, School of Medicine) for critically reading the manuscript and his suggestions. We are also grateful to the numerous nurses (Dr. Sardjito Hospital), Sri Fatmawati (Faculty of Medicine, UGM), and Maria X. Sosa (Johns Hopkins University, School of Medicine) for technical assistance, Courtney Berrios (Johns Hopkins University, School of Medicine) and Harini Natalia (Faculty of Medicine, UGM) for IRB management. The genotyping analyses reported here were performed at the Center for Complex Disease Genomics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. This work was supported by the grant from DIKTI-FULBRIGHT Senior Research Program (2012) (G.).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Gunadi, Makhmudi, A., Agustriani, N. et al. Effects of SEMA3 polymorphisms in Hirschsprung disease patients. Pediatr Surg Int 32, 1025–1028 (2016). https://doi.org/10.1007/s00383-016-3953-7
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DOI: https://doi.org/10.1007/s00383-016-3953-7