Genome-wide association study of homocysteine levels in Filipinos provides evidence for CPS1 in women and a stronger MTHFR effect in young adults

Year: 2010

Type: article

Abstract: Plasma homocysteine (Hcy) level is associated with cardiovascular disease and may play an etiologic role in vascular damage, a precursor for atherosclerosis. We performed a genome-wide association study for Hcy in 1786 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). The most strongly associated single-nucleotide polymorphism (SNP) (rs7422339, P = 4.7 x 10(-13)) encodes Thr1405Asn in the gene CPS1 and explained 3.0% of variation in the Hcy level. The widely studied MTHFR C677T SNP (rs1801133) was also highly significant (P = 8.7 x 10(-10)) and explained 1.6% of the trait variation. We also genotyped these two SNPs in 1679 CLHNS young adult offspring. The MTHFR C677T SNP was strongly associated with Hcy (P = 1.9 x 10(-26)) and explained approximately 5.1% of the variation in the offspring. In contrast, the CPS1 variant was significant only in females (P = 0.11 in all; P = 0.0087 in females). Combined analysis of all samples confirmed that the MTHFR variant was more strongly associated with Hcy in the offspring (interaction P = 1.2 x 10(-5)). Furthermore, although there was evidence for a positive synergistic effect between the CPS1 and MTHFR SNPs in the offspring (interaction P = 0.0046), there was no significant evidence for an interaction in the mothers (P = 0.55). These data confirm a recent finding that CPS1 is a locus influencing Hcy levels in women and suggest that genetic effects on Hcy may differ across developmental stages.

Source: Human Molecular Genetics

DOI: 10.1093/hmg/ddq062

Authors: Leslie A. Lange, Damien C. Croteau-Chonka, Amanda F. Marvelle, Li Qin, Kyle J. Gaulton, Christopher W. Kuzawa, Thomas W. McDade, Yunfei Wang, Yun Li, Shawn Levy, Judith B. Borja, Ethan M. Lange, Linda S. Adair, Karen L. Mohlke

Institutions: University of North Carolina at Chapel Hill, Northwestern University, Vanderbilt University, University of San Carlos

Language: English

Topic: Folate and B Vitamins Research

Subfield: Rheumatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, Directorate for Biological Sciences, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development

OpenAlex ID: W2129606441