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 × 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 × 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 × 10-26) and explained ~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 × 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.
Original language | English (US) |
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Article number | ddq062 |
Pages (from-to) | 2050-2058 |
Number of pages | 9 |
Journal | Human molecular genetics |
Volume | 19 |
Issue number | 10 |
DOIs | |
State | Published - Feb 13 2010 |
Funding
This work was supported by National Institutes of Health grants (DK078150, TW05596, HL085144), pilot funds (RR20649, ES10126 and DK56350) and training grants (T32 GM007092 to D.C.C.-C., T32 HL69768 to A.F.M.). K.L.M. is a Pew Scholar in the Biological Sciences.
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Genetics(clinical)