Effects of SEMA3 polymorphisms in Hirschsprung disease patients

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.

Three variants were analyzed in 60 non-syndromic HSCR patients and 118 ethnicity-matched controls for association studies by genotyping.

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.

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.