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Elevated Homocysteine, Heart Disease Link Questioned

Robert Clarke, M.D., from the University of Oxford in the United Kingdom, and colleagues performed a meta-analysis of 19 unpublished datasets (48,175 coronary heart disease cases and 67,961 controls) and 86 published datasets (28,617 cases and 41,857 controls). Individuals had been genotyped for multiple genetic variants, including the methylene tetrahydrofolate reductase C677T gene variant, with the TT variant associated with elevated homocysteine levels.

Considering the unpublished studies, the researchers found that, comparing TT versus CC homozygotes, the case-control odds ratio for heart disease was 1.02 (95 percent confidence interval [CI], 0.98 to 1.07; P = 0.28) overall, and 1.01 (95 percent CI, 0.95 to 1.07) in unsupplemented low-folate populations. In contrast, for the published studies, the odds ratio was significantly higher, at 1.15. Within the published studies, the odds ratio was 1.12 for the 14 larger studies (13,119 cases) and 1.18 for the 72 smaller studies (15,498 cases).

"The CI for the overall result from large unpublished datasets shows lifelong moderate homocysteine elevation has little or no effect on coronary heart disease," Clarke and colleagues conclude. "The discrepant overall result from previously published studies reflects publication bias or methodological problems."

Several of the authors are employees of Unilever R&D Vlaardingen. One author is an employee of deCode.

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Elevated homocysteine levels are not associated with a greater risk of coronary heart disease when considering unpublished data, suggesting publication bias, according to a study available online Feb. 21 in PLoS Medicine.

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