rs4998557

A candidate gene association study of 610 families (329 trios and 281 duos) from the US and Canada investigating 17 SNPs in SOD1 and SOD2 genes for association with nonsyndromic myelomeningocele (MM). Four SOD1 SNPs (rs202446, rs202447, rs4816405, rs2070424) and one SOD2 SNP (rs5746105) showed significant association with MM (p<0.05), with rare alleles appearing protective. Gene expression analysis in CEPH cell lines suggested associations with altered SOD1 and SOD2 mRNA levels.

This study demonstrates a genetic interaction between the RET enhancer polymorphism rs2435357 (C>T) on chromosome 10 and chromosome 21 dosage in Down syndrome and Hirschsprung disease. The RET +9.7 T allele showed significant association with HSCR in both transmission disequilibrium (P=0.0015) and case-control (P=0.0115) analyses, with allele frequencies of 0.26 in DS alone, 0.61 in HSCR alone, and 0.41 in DS+HSCR, representing the first reported genetic interaction between a common functional variant and chromosome 21 dosage in human developmental disorders.

A study of 865 meningomyelocele (MM) patients recruited from six sites in North America (45.9% Hispanic Mexican, 36.2% Caucasian) to identify genetic risk factors for spina bifida using transmission disequilibrium testing. The researchers identified maternal MTHFR 667T allele as a risk factor and found genes involved in glucose transport and metabolism as potential risk factors for MM.