Homocysteine metabolism in families from southern Italy with neural tube defects: role of genetic and nutritional determinants

Objective To evaluate the role of different polymorphic gene variants involved in homocysteine metabolism and plasma levels of homocysteine, folate and vitamin B12 in families from southern Italy with neural tube defects (NTDs). Methods Eighteen fathers, 15 NTD children and 60 women who had conceived NTD foetuses were investigated. A group of 100 adults and 43 apparently healthy children was used as control. At the time of blood draw, none were taking vitamin pills or nutritional supplements. Results Among controls, 79 (55.2%) were heterozygous for C677T MTHFR variant and 26 (18.2%) were TT homozygous. Among the cases, 35 (61.4%) out of 57 mothers and 7 (38.9%) out of 18 fathers carried the T allele; 12 (21.1%) mothers and 2 (11.1%) fathers had the TT genotype. Four (26.7%) out of 15 probands were TT homozygous and 11 (73.3%) were heterozygous (Fisher exact test p = 0.025). No significant difference between groups was observed for the 1298C MTHFR variant and CBS haplotypes. Median homocysteine in NTD children was significantly higher (10.0 mu mol/L) than that of controls (median 4.5 mu mol/L, Mann-Whitney p < 0.05). Folate and B12 were not different among groups. Conclusions The T677 MTHFR allele is significantly associated with the occurrence of NTDs; no significant association has been observed with other genetic determinants analysed. Homocysteine levels in children with NTDs are significantly higher than those of the paediatric population from the same geographical area. Copyright (c) 2006 John Wiley & Sons, Ltd.