OBJECTIVES: To investigate the association of polymorphisms in complement factor H (CFH) and coronary heart disease (CHD) using meta-analysis. BACKGROUND: Age-related macular degeneration (AMD) and CHD may share partially overlapping pathogenesis. A non-synonymous SNP (rs1061170/Y402H) in CFH encoding complement factor H (fH) is robustly associated with increased AMD risk but associations with CHD risk have been inconsistent. METHODS: We conducted de novo genotyping and genetic association analyses of incident and prevalent CHD in four studies, and in silico analysis of the same association in a further four cohorts. We pooled these data with information from all published studies using random effects meta-analysis, including a total of 48,646 participants of which 9097 were CHD cases. We also evaluated the association of Y402H with known risk factors for CHD by pooling results from new and in silico studies providing relevant data. RESULTS: CFH genotype was not associated with CHD. Compared to the reference TT homozygote group the pooled odds ratio (OR) for individuals homozygous for the C allele was 1.02, 95% CI (0.91, 1.13) and that for heterozygote TC individuals was 1.04 (0.98, 1.10). There was no association of CFH with systolic and diastolic blood pressure, total-, LDL- and HDL-cholesterol, or body mass index. Individuals who were CC compared to TT had higher triglyceride levels: pooled mean difference 0.06 (0.02, 0.10) mmol/L, p=0.005. CONCLUSIONS: The AMD-associated CFH genotype is not associated with CHD. With the possible exception of triglycerides, this CFH SNP was not associated with a wide range of other CHD risk factors.
OBJECTIVES: To investigate the association of polymorphisms in complement factor H (CFH) and coronary heart disease (CHD) using meta-analysis. BACKGROUND: Age-related macular degeneration (AMD) and CHD may share partially overlapping pathogenesis. A non-synonymous SNP (rs1061170/Y402H) in CFH encoding complement factor H (fH) is robustly associated with increased AMD risk but associations with CHD risk have been inconsistent. METHODS: We conducted de novo genotyping and genetic association analyses of incident and prevalent CHD in four studies, and in silico analysis of the same association in a further four cohorts. We pooled these data with information from all published studies using random effects meta-analysis, including a total of 48,646 participants of which 9097 were CHD cases. We also evaluated the association of Y402H with known risk factors for CHD by pooling results from new and in silico studies providing relevant data. RESULTS: CFH genotype was not associated with CHD. Compared to the reference TT homozygote group the pooled odds ratio (OR) for individuals homozygous for the C allele was 1.02, 95% CI (0.91, 1.13) and that for heterozygote TC individuals was 1.04 (0.98, 1.10). There was no association of CFH with systolic and diastolic blood pressure, total-, LDL- and HDL-cholesterol, or body mass index. Individuals who were CC compared to TT had higher triglyceride levels: pooled mean difference 0.06 (0.02, 0.10) mmol/L, p=0.005. CONCLUSIONS: The AMD-associated CFH genotype is not associated with CHD. With the possible exception of triglycerides, this CFH SNP was not associated with a wide range of other CHD risk factors.
Authors: David Weismann; Karsten Hartvigsen; Nadine Lauer; Keiryn L Bennett; Hendrik P N Scholl; Peter Charbel Issa; Marisol Cano; Hubert Brandstätter; Sotirios Tsimikas; Christine Skerka; Giulio Superti-Furga; James T Handa; Peter F Zipfel; Joseph L Witztum; Christoph J Binder Journal: Nature Date: 2011-10-05 Impact factor: 49.962
Authors: Andreas Jönsen; Sara C Nilsson; Emma Ahlqvist; Elisabet Svenungsson; Iva Gunnarsson; Karin G Eriksson; Anders Bengtsson; Agneta Zickert; Maija-Leena Eloranta; Lennart Truedsson; Lars Rönnblom; Gunnel Nordmark; Gunnar Sturfelt; Anna M Blom Journal: Arthritis Res Ther Date: 2011-12-15 Impact factor: 5.156