Interaction of homocysteine and conventional predisposing factors on risk of ischaemic stroke in young people: consistency in phenotype-disease analysis and genotype-disease analysis. Issue 10 (19th April 2006)

• Record Type: Journal Article
• Authors: Pezzini, A; Grassi, M; Del Zotto, E; Assanelli, D; Archetti, S; Negrini, R; Caimi, L; Padovani, A
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 77:Issue 10(2006)
• Page Start: 1150
• Page End: 1156
• Publication Date: 2006-04-19
• Subjects: CART, classification and regression trees -- MTHFR, methylenetetrahydrofolate reductase gene -- tHcy, total homocysteine; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp.2005.076083
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background and objectives: Whether the association between mild hyperhomocysteinaemia and ischaemic stroke is the consequence of a predisposing genetic background or is due to the confounding influence of established predisposing factors remains to be determined. Methods: Plasma total homocysteine (tHcy) concentration and the distribution of the C 677 T genotypes of the methylenetetrahydrofolate reductase gene ( MTHFR ) were compared in 174 consecutive patients with stroke aged <45 years and 155 age and sex-matched controls. The effect of conventional risk factors on the relationship between phenotype-disease and genotype-disease was analysed by two-way and three-way interaction analysis and by the classification and regression trees (CART) model. Results: tHcy concentrations were markedly higher in patients with ischaemic stroke (median 11.9 μmol/l, range 2.0–94.0) than in controls (median 9.8 μmol/l, range 4.7–49.6). An increased risk was also associated with the TT 677 genotype (odds ratio (OR) 1.98; 95% confidence interval (CI) 1.04 to 3.78) and with the T allele (1.40; 95% 1.03 to 1.92) of the MTHFR gene. A differential effect of Hcy levels on risk of stroke was observed according to the distribution of environmental–behavioural risk factors, with a stronger influence in the subcategory of people with hypertension and smokers (OR 24.8; 95% CI 3.15 to 196). A comparable environmental-dependent TT 677 MTHFR genotype–stroke association was observed in the genotype-disease analysis. Conclusions: A consistency of phenotype-disease analysis and genotype-disease analysis is indicated by analysing specific subcategories of patients, defined by the distribution of established risk factors. The assumption that the Hcy–stroke relationship is unlikely due to a reverse-causality bias is indirectly supported by our data.