C4B*Q0 allotype as risk factor for myocardial infarction

Kramer, J.; Rajczy, Katalin; Hegyi, Lajos; Fülöp, Tamás; Mohácsi, Attila; Mezei, Zsuzsa; Keltai, Mátyás; Blaskó, George; Ferenczy, E; Anh-Tuan, Nguyen; Füst, George

doi:10.1136/bmj.309.6950.313

Cited by 38 publications

(32 citation statements)

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“…The frequencies of the two most interesting C3 and C4 alleles (18), the first lying in the vicinity of the apolipoprotein E gene locus on chromosome 19 and the latter in the vicinity of the steroid 21-hydroxylase gene locus on chromosome 6 ware also determined and related to lipid properties. In the study group the frequencies of C3-S and C3-F were 0.84 and 0.16, respectively, identical to those found in the healthy population.…”

Section: Resultsmentioning

confidence: 99%

“…Internal quality control was evaluated throughout the study with the use of on the one hand 7a#-DNA polymerase and template DNA-free samples, and on the other, intra-and inter-observer crossover investigation. C3 and C4 (the third and fourth complement of the human complement system) phenotypes were determined by high voltage electrophoresis using the method of Teisberg (24,18).…”

Section: Measurement Of Lipids Lipoproteins and Apolipoproteinsmentioning

confidence: 99%

“…C3 levels measured in sera from subjects without previous ischaemic events are independently associated with the risk of myocardial infarction (17). A certain C4 allotype (C4B*QO) had higher prevalence in men with myocardial infarction (18). C3 was reported to be involved in the regulation of the adipsin/acylation stimulating protein system which seems to play a pivotal role in regulation of triacylglycerol removal from plasma (19).…”

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confidence: 99%

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Apolipoprotein E and Complement C3 Polymorphism and Their Role in the Response to Gemfibrozil and Low Fat Low Cholesterol Therapy

Németh

Szakmary

Kramer

et al. 1995

CCLM

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Summary:Three different allelic variants of apolipoprotein E determine, in concert with other gene products, the levels of plasma lipoproteins. Recently, cleavage products of the complement C3 molecule have also been implicated in determining plasma triacylglycerol concentrations.This study presents data of an ongoing study to dissect the role of the apolipoprotein E gene locus in the response to low fat/low cholesterol diet combined with gemfibrozil treatment. In addition, for the first time, the significance of C3 allelic variants to such hypolipidaemic therapy response was analysed. To this end data from 81 obese hyperlipoproteinaemic patients (Fredrickson type II/A and B and type IV and V) confirmed the usefulness of the combined gemfibrozil/diet treatment and unveiled apolipoprotein E allele group specific therapy responses. The mean changes of lipid properties due to combined treatment was 15% for total cholesterol, 48% for triacylglycerols and 28% for atherogenic index. Division into hyperlipidaemia types according to Fredrickson and subgrouping into E2, E3 and E4 groups (apolipoprotein E2/2 and 2/3, apolipoprotein E3/3 and apolipoprotein E4/2 and 4/3 phenotype groups respectively) exposed pronounced differences from these mean changes, suggesting substantial influence of apolipoprotein E variants on this therapy. We observed triacylglycerol reductions of from 17% in type IIA-apolipoprotein E3 group patients up to 78% in the type IV and V-apolipoprotein E2 group. Thus it might be concluded the apolipoprotein E genotyping aides therapy success prediction. Although, low sample numbers in some subgroups obscures significance in this pilot study, significant therapy success emerges for the E3 and E4 group in type IV and V hyperlipidaemia and type IIB-apolipoprotein E3 homozygous patients can be predicted to respond better than apolipoprotein E2 carriers.Finally, we present evidence that positive changes of lipid properties are also determined by the "fast" complement C3 allel (C3-F). Patients with complement factor C3-FS pattern respond better to treatment than patients with C3-SS configuration, In summary these data endorse the genotyping of apolipoprotein E alleles to predict maximal success of "fibrate" treatment. In addition they argue strongly for further assessment of the involvement of complement C3 allelic variations in lipid homeostasis.

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Section: Resultsmentioning

confidence: 99%

Section: Measurement Of Lipids Lipoproteins and Apolipoproteinsmentioning

confidence: 99%

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confidence: 99%

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Apolipoprotein E and Complement C3 Polymorphism and Their Role in the Response to Gemfibrozil and Low Fat Low Cholesterol Therapy

Németh

Szakmary

Kramer

et al. 1995

CCLM

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“…Thus, it is suggested that genes at these regions confer susceptibility to disease and that these regions can be a challenge for the identification of candidate genes for MI. In bin 6.2, the first most important region for MI, are located various known genes (MOG, HSPA1A, LTA, TNF, AGER, HFE, HLA-DR and C4) with a possible implication to MI (Ozaki et al 2002;McCarthy et al 2004;Bolla et al 1998;Koch et al 2001;Hofmann et al 2005;Tuomainen et al 1999;Sperti et al 2000;Kramer et al 1994). Bin 14.1 is the region where genes CAQ14 and PSMA6 are located.…”

Section: Discussionmentioning

confidence: 99%

Identification of chromosomal regions linked to premature myocardial infarction: a meta-analysis of whole-genome searches

Ζιντζαράς

Kitsios

2006

J Hum Genet

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Myocardial infarction (MI) is a complication of coronary artery disease and the leading cause of death in the Western world. MI is considered a distinct phenotype with an increased genetic component for its premature type. MI's exact inheritance pattern is still unknown. Genome searches for identifying susceptibility loci for premature MI produced inconclusive or inconsistent results. Thus, a genome search metaanalysis (GSMA) was applied to available genome search data on premature MI. GSMA is a non-parametric method to identify genetic regions that rank high, on average in terms of linkage statistics across genome searches unweighted or weighted by study size. The significance of each region's average and heterogeneity, unadjusted or adjusted by neighbouring average simulated ranks, was calculated using a Monte Carlo test. The meta-analysis involved five genome searches in Caucasians. 3) were found to have significant average rank by either unweighted or weighted analyses. In addition, region 8q24.21-8q24.3 produced significant low heterogeneity (P unadjusted =0.03 and P adjusted =0.05). Four regions (6p22.3-6p21.1, 14p13-14q13.1, 8q13.2-8q22.2, 8q24.21-8q24.3) were not identified by the individual studies. The meta-analysis suggests that these four regions should be further investigated for genes that confer susceptibility to MI.

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“…9 The C4B*Q0 allele was found with increased frequency among myocardial infarction patients aged 60 to 79 years compared with age-matched healthy controls. 9 Moreover, in C4B*Q0 carriers myocardial infarction had a significantly higher risk for lethal outcome compared with noncarriers. 9 Recently we also found the frequency of the C4B*Q0 carriers to be significantly increased in Icelandic CHD patients.…”

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confidence: 99%

Frequencies of Certain Complement Protein Alleles and Serum Levels of Anti–Heat-Shock Protein Antibodies in Cerebrovascular Diseases

Kramer

Harcos

Prohászka

et al. 2000

Stroke

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Background and Purpose-A strong correlation exists between the intensity of atherosclerotic alterations in different arteries. Marked differences exist, however, in the age and sex distribution and risk factors for coronary heart disease (CHD) and cerebrovascular disease (CVD). We therefore performed genetic and immunologic studies in patients with CVD. Methods-We studied 292 patients with CVD (stroke or transient ischemic attack) and as control either 198 healthy blood donors and 485 healthy elderly (aged Ͼ60 years) people (genetic study) or 94 blood donors aged 45 to 60 years and 49 healthy elderly (aged Ͼ60 years) people (anti-heat-shock protein [hsp] measurements). Allele frequencies of 3 genes (C4A, C4B, and C3) encoding proteins of the complement system were determined by electrophoresis and immunofixation. Serum concentration of autoantibodies against 60-kDa heat-shock protein (anti-hsp60) was measured by the enzyme-linked immunosorbent assay method. Results-Marked differences were observed between CVD patients and controls in the genetic studies. In the CVD patients aged Ͼ60 years, the frequency (11.3%) of the deficient allele of the C4B gene (C4B*Q0) was significantly (Pϭ0.0003) higher than that of the healthy controls (5.4%). By contrast, in the group aged 45 to 60 years, the frequency of the C4B*Q0 allele was lower in patients than in controls. Serum concentration of anti-hsp60 in the CVD patients did not differ from control values. Conclusions-In previous studies C4B*Q0 frequency was reported to be higher in CHD patients aged 45 to 60 years than in aged-matched controls. Moreover, high anti-hsp60 levels were found in CHD patients. These findings contrast with our present report of lower frequency of C4B*Q0 in CVD patients. Therefore, genetic and immunologic factors may at least partly explain the differences between the natural history and risk factors of CHD and CVD. (Stroke.

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C4B*Q0 allotype as risk factor for myocardial infarction

Cited by 38 publications

References 4 publications

Apolipoprotein E and Complement C3 Polymorphism and Their Role in the Response to Gemfibrozil and Low Fat Low Cholesterol Therapy

Apolipoprotein E and Complement C3 Polymorphism and Their Role in the Response to Gemfibrozil and Low Fat Low Cholesterol Therapy

Identification of chromosomal regions linked to premature myocardial infarction: a meta-analysis of whole-genome searches

Frequencies of Certain Complement Protein Alleles and Serum Levels of Anti–Heat-Shock Protein Antibodies in Cerebrovascular Diseases

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