Locke et al. performed a case-control study in a group of 121 American case families (mother, father, and proband with DS and AVSD) and 122 American control families (mother, father, and proband with DS and no CHD), all genotyped for 45 polymorphisms in MTHFR, MTR, MTRR, RFC1, and CBS genes, observing that several RFC1 polymorphisms, all in strong linkage with the RFC1 80G>A one, showed nominally significant associations with AVSD, with ORs of between 1.34 and 3.78. The gene discussed is RFC1; the disease is familial atrioventricular septal defect.