Papers

C4B*Q0 allotype as risk factor for myocardial infarction

BMJ 1994; 309 doi: https://doi.org/10.1136/bmj.309.6950.313 (Published 30 July 1994) Cite this as: BMJ 1994;309:313
  1. J Kramer,
  2. K Rajczy,
  3. L Hegyi,
  4. T Fulop,
  5. A Mohacsi,
  6. Z Mezei,
  7. M Keltai,
  8. G Blasko,
  9. E Ferenczy,
  10. N Anh-Tuan,
  11. G Fust
  1. Department of Immunopathology, National Institute of Haematology, Blood Transfusion, and Immunology, PO Box 44, Budapest H-1502
  2. Hungary Institute for Gerontology, Semmelweis University Medical School, Budapest Szent Imre Hospital, Budapest 1st Department of Medicine, University Medical School, Debrecen Szent Istvan Hospital, Budapest Hungarian Institute of Cardiology, Budapest
  1. Correspondence to: Dr Kramer
  • Accepted 3 March 1994

The prevalence of the deficient, silent allotype of the C4B gene (C4B*Q0) is lower in elderly than in young healthy people, particularly in men.1 This may reflect increased mortality from some disease in middle aged carriers of the C4B*Q0 gene. We determined the presence of the gene in patients with acute myocardial infarction because myocardial infarction is the leading cause of death among middle aged Hungarians.

Patients, methods, and results

We studied 181 consecutive patients with confirmed Q wave myocardial infarction admitted to four hospital departments between June 1992 and January 1993 (125 men, 56 women, aged 42-78), 93 consecutive patients with symptoms of angina pectoris (65 men, 28 women; aged 43-62) who were examined by coronary angiography (coronarography), and 737 previously tested healthy controls (252 young people aged 22-45 and 485 elderly people aged 60-99).1 Myocardial infarction was diagnosed as typical chest pain lasting at least one hour, an ST segment elevation of at least 1 mm in an electrocardiogram, and typical cardiac enzyme values. We diagnosed inferior and anterior wall infarction in 103 and 70 patients, respectively; in eight patients the localisation of the infarct was uncertain.

We took blood samples from the patients with myocardial infarction within 24 hours of admission and sent them immediately to the laboratory in tubes containing EDTA. Plasma samples were stored at −70°C until tested. C4 allotyping was performed with high voltage electrophoresis, followed by immunofixation with human C4 antibody (Atlantic Antibodies).2,3 We determined aspartate aminotransferase and alanine aminotransferase values serially with commercially available kits (Boehringer Mannheim, Germany). In order to exclude patients with enzyme elevations unrelated to myocardial infarction, we evaluated peak aspartate aminotransferase values only in patients whose alanine aminotransferase values had not increased concomitantly. Patients with raised aspartate aminotransferase values at the first determination were also excluded from the further evaluation.

The prevalence of C4 allotypes was significantly higher in patients with myocardial infarction than in the healthy elderly controls (27.6% v 10.7%; P<0.0001) - the only significant difference between the patients and the controls. After age matching, which was possible only in those aged 60-79, 38% (24/63) of male patients and 8% (10/133) of healthy men carried the C4B*Q0 allotype (P<0.0001). The odds ratio of a 60-79 year old man with acute myocardial infarction being a C4B*Q0 carrier compared with his healthy counterpart was 7.57 (95% confidence interval 3.31 to 17.2); in women this odds ratio was 0.84 (0.33 to 2.16).

The C4B*Q0 carrier state influenced the outcome of myocardial infarction (table). The odds ratio of dying was significantly higher for men who carried the gene compared with those who did not (18.0 (2.1 to 153) in homozygous men and 5.53 (1.21 to 25.4) in heterozygous men). Data on women were insufficient to calculate odds ratios.

Outcome of Q wave myocardial infarction in patients with or without C4B*Q0 allotype

View this table:

Average peak aspartate aminotransferase values were significantly higher in patients who carried the C4B*Q0 gene than in those who did not (218 U/ml (median 195 U/ml, range 20-635 U/ml) v 145 U/ml (median 120 U/ml, range 12-506 U/ml; P=0.040 by Mann-Whitney U test). Similarly, the proportion of patients with a peak aspartate aminotransferase value greater than 200 U/ml was significantly higher in those who carried the C4B*Q0 gene (52.7% v 26.5%; X2 <0.01). Coronarography did not show any difference in the severity of coronary heart disease according to presence of the C4B*Q0 gene.

Comment

We found that the prevalence of the C4B*Q0 gene was higher in men with myocardial infarction than in controls and that peak aspartate aminotransferase values and mortality from infarction were higher among those who carried the gene than among those who did not. The extent of myocardial infarction is related to peak aspartate aminotransferase values,4 and both early and late (up to five years) mortality are adversely affected by increased size of infarct.5 The C4B*Q0 allotype therefore seems to be associated with a poor prognosis after infarction. We conclude that people who carry the gene have a shorter life expectancy,1 partly because of their higher mortality from myocardial infarction, the leading cause of death among middle aged and elderly Hungarians.

This work was supported by the National Scientific Research Foundation (OTKA 211). We thank Peter Vargha (Semmelweis University Medical School, Budapest) for his help in statistical analysis.

References

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