The common Y402H variant in complement factor H gene is not associated with susceptibility to myocardial infarction and its related risk factors

Abstract

Recently, the genetic variant Y402H in the CFH (complement factor H) gene was associated with an increased risk for MI (myocardial infarction) in a prospective Caucasian cohort. In another nested case-control study, however, the CFH-Y402H variant did not carry susceptibility to MI. The aim of the present study was to test for an association between the CFH-Y402H variant and MI in a large case-control sample with a familial background for CAD (coronary artery disease). A total of 2161 individuals from the German MI family study were studied by questionnaire, physical examination and biochemical analyses. MI patients (n=1188; 51.4+/-8.6 years at first MI) were recruited from families with at least two members affected by MI and/or severe CAD. Spouses, sisters-in-law and brothers-in-law respectively, without MI/CAD were included as unaffected controls (n=973; 56.9+/-9.8 years). Genotyping was performed using a TaqMan assay. The common Y402H variant in the CFH gene was not associated with classical cardiovascular risk factors (diabetes, hypercholesterolaemia, hypertension, obesity, smoking and C-reactive protein serum levels). No association was found between the CFH-Y402H variant and susceptibility to MI. Separate analyses in both men and women revealed no gender-specific influence of the gene variant on cardiovascular risk factors or MI. This investigation was unable to replicate the association between the common CFH-Y402H variant and susceptibility to MI in our large Caucasian population which is enriched for genetic factors. We conclude that the CFH-Y402H variant has no relevant risk-modifying effect in our population.

Genetics of C-reactive protein and complement factor H have an epistatic effect on carotid artery compliance: The Cardiovascular Risk in Young Finns Study

“…A deleterious effect of the CFH 402His allele on CVD has recently been reported in three population‐based studies [8–10], whereas in some case‐control studies, no association between the CFH Tyr402His polymorphism and atherothrombotic events was detected [11,12,23]. To the best of our knowledge, the current study is the second one to assess the interplay between CRP and CFH genetics on cardiovascular traits.…”

Association between PPARα gene polymorphisms and myocardial infarction

“…At recruitment, all patients were studied by comparable design as previously described including a standardized interview, clinical examination and biochemical as well as molecular analyses either at a visit to the study centre (patients from the MONICA Augsburg study) or at a home visit by a physician (patients from rehabilitation centres) [12,14,15]. Validation of cardiovascular events at study entry was performed by a review of medical records.…”

A vital role for complement in heart disease

“…Factor H is a complement regulator, and polymorphisms, especially Y402H, in the Factor H-gene is extensively studied and associated with age-related macular degeneration (Gehrs et al, 2010). There are conflicting results about the Y402H polymorphisms and cardiovascular disease including myocardial infarction, but most studies find no association, so the importance of factor H variants in cardiovascular disease at present is unclear (Zee et al, 2006;Kardys et al, 2006;Nicaud et al, 2007;Stark et al, 2007;Sofat et al, 2010). Thus, some variants in genes encoding proteins of the complement system including MBL and C3 are associated with risk for coronary heart disease, while in others like factor H appear to be more uncertain.…”