CC chemokine receptor 5 (CCR5) deletion polymorphism does not protect Czech males against early myocardial infarction

Dear Sir, Polymorphisms in genes coding for CC chemokine receptors, CCR2 and CCR5, have been studied as genetic markers of coronary artery disease (CAD) [1–5]. Whilst the VI genotype of the CCR2 V64I polymorphism has been implicated in the manifestation of myocardial infarction (MI) in different populations [1–3], the data on possible involvement of the CCR5 deletion variant in ethiopathogenesis of coronary atherosclerosis are conflicting [4, 5]. A protective effect of CCR5D32 allele against early MI was reported in Spanish males [4]. However, a recent study from the LURIC (Ludwigshafen Risk and Cardiovascular Health) cohort of male and female German patients with CAD did not show any difference between CCR5D32 frequencies in cases and controls [5]. We have, therefore, decided to replicate [6] the original study [4] in our Czech cohort of male patients with early occurrence of MI. Into our association study we enrolled 80 cases – Czech males, who had their first MI before the age of 55 years; MI was diagnosed according to the international consensus [7]. The controls comprised 247 healthy Czech males (blood donors), in whom cardiovascular symptomatology was excluded by questionnaire emphasizing family history of cardiovascular disease. Informed consent was obtained from all study participants and ethical committee approved the study. Genotyping methodology [polymerase chain reaction-sequence specific primers (SSP)] was described previously [8]. Significance of differences in CCR5D32 allele and genotype frequencies between cases and controls was assessed by standard 2 · 2 chi-square analysis using SIGTEST, a computer-based statistical programme that uses a Woolf-Haldane correction in cases of small numbers [8]. Both control and patient populations were in Hardy–Weinberg equilibrium with regard to the genotypes distribution (P > 0.05). Frequency of the CCR5D32 allele in Czech males with early MI did not differ from the frequency in control subjects (Table 1, first row). There was one homozygous individual (CCR5D32/CCR5D32) present amongst the patients (1.3%) and also one such individual appeared within controls (0.4%). The original statement about protective role of CCR5D32 variant in MI was based on less frequent occurrence of the deletion allele in male patients with early MI (Table 1, second row) and also on absence of CCR5D32 homozygous individuals amongst Spanish patients [4]. Studies of several chemokine polymorphisms including CCR5, which were performed in German [5] and also Hungarian [9] patients with CAD, did not, however, find significant relationship between CCR5D32 and CAD (see Table 2 for gene frequencies in these two populations). Interestingly, the German study in the LURIC cohort did not confirm CCR5D32-associated protection against premature MI, although no frequency data or the age limit for early MI was reported [5]. Despite both aforementioned negative studies [5, 9] have been performed in big cohorts of CAD patients, their data cannot be fully compared with the findings of the original Spanish study, which was limited to males with/without MI [4]. Cases and controls in both German and Hungarian studies comprised both sexes, in a range from 24% to 48% females [5, 9]. Although there have been no reports of differential distribution of CCR5D32 allele between healthy males and females and also our own data does not favour gender distinction [CCR5D32 allele frequency; males (n 1⁄4 247), 11.1%; females (n 1⁄4 139), 10.1%; P 1⁄4 0.7], intrinsic or external factors in complex disease may cause increased occurrence of particular allele and/or genotype in patients of either sex. With aim to replicate the original study of CCR5D32 protective effect [4] as closely as possible we have designed our association study in Czech population accordingly: using only male cohorts we Journal of Internal Medicine 2005; 257: 564–566