Homocysteine levels in A/J and C57BL/6J mice: genetic, diet, gender, and parental effects. Physiol Genomics 21

Increased levels of homocysteine in the blood have been associated with various birth defects and adult diseases. However, the extent to which genetic factors control homocysteine levels in healthy individuals is unclear. Laboratory mice are valuable models for dissecting the genetic and environmental controls of total homocysteine (tHcy) levels. We assessed the inheritance of tHcy levels in two inbred strains, A/J and C57BL/6J (B6), under controlled physiological conditions and assessed the relative importance of genetic, diet, gender and parental effects. Diet affected mean tHcy levels whereas gender affected both mean and variance of tHcy levels. Moreover, gender of the parents influenced mean tHcy levels in reciprocal F1 hybrids suggesting maternal effects. Finally, gene-diet interactions affected heritability of mean tHcy levels. These studies showed that each of these factors contribute to tHcy levels and provided important clues to understanding homocysteine homeostasis in humans. 4INTRODUCTION Hyperhomocysteinemia, or elevated levels of total homocysteine (tHcy) in the blood, is an independent risk factor for neural tube defects (NTDs) (14, 37), vascula