Atherosclerosis 152 (2000) 257 – 258
Letter to the Editor
www.elsevier.com/locate/atherosclerosis
Apolipoprotein B signal peptide polymorphism in relation to lipids and diabetes in male CAD patients
Previous studies reported inconsistent data concern-ing an association between the apolipoprotein B (apo B) signal peptide insertion/deletion (Ins/Del) polymor-phism and coronary artery disease (CAD) or myocar-dial infarction [1]. Our group found an association between the Del allele and CAD in nondiabetic Czech males under 55 years of age [2]. In addition to problems posed by the selection of control groups, as well as by differences in the disease definition and in ethnic back-ground discussed by Marshall et al. [3], other factors such as the presence or absence of type 2 diabetes mellitus might also partially explain some inconsisten-cies of the previous association studies, e.g. the apo B Ins/Del polymorphism was associated with 2-h and fasting plasma glucose level [4,5].
To test the possible influence of type 2 diabetes, we analyzed a group of male patients with angiographi-cally proven CAD according to the standard criteria [6]. Subjects were recruited consecutively from the Cen-ter of Cardiovascular Surgery and Transplantation in Brno and from the Department of Cardiopulmonary Testing, University Hospital Brno-Bohunice in a period from August 1996 to October 1998. Allele frequencies of the polymorphism mentioned above were ascertained by PCR methods [7] in 515 patients [Caucasians, mean age 57.6598.25 years, 348 (67.6%) of them with hyper-tension, 135 (26.2%) with type 2 diabetes mellitus, without valvular diseases or cardiomyopathies]. In or-der to contribute to the still open question of a relation-ship of the studied polymorphism with CAD, fasting plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-low-density lipoprotein cholesterol (HDL), triglycerides (TG), apo B and apo AI were measured as described elsewhere [8]. The data for TC, TG, LDL, HDL were available from 252 patients without hypolipidemic therapy, and for apo B and apo AI from 219 of these patients.
Allele frequencies (genotypes) in the total sample were 65.6% for Ins and 34.4% for Del alleles (220 Ins/Ins, 236 Ins/Del, 59 Del/Del). We found a signifi-cant association between this polymorphism and the plasma concentration of TC [P=0.05, Kruskal – Wallis
ANOVA (K – W ANOVA)], LDL (PB0.05, K – W ANOVA) and apo B (PB0.05, K – W ANOVA) in patients without hypolipidemic therapy. The respective mean plasma concentration values in patients with Ins/
Ins, Ins/Del and Del/Del genotypes were 5.6190.89; 5.7491.11; 6.1691.28 mmol/l for TC, 3.4090.84; 3.5290.91; 3.9191.05 mmol/l for LDL, and 1.139
0.21; 1.1690.26; 1.2790.25 g/l for apo B. In agree-ment with previous studies, our results thus confirm the relation between the Ins/Del polymorphism in the sig-nal peptide of the apo B gene and variations in plasma lipoprotein and apolipoprotein levels [1].
In the whole sample, we observed that allele frequen-cies of the polymorphism studied tended to be different between CAD patients with and without type 2 diabetes mellitus, with a higher frequency of the Ins allele in the diabetics (69.7 vs. 64.2%; P=0.06, Fisher’s exact test). This finding is consistent with the studies of Kammerer et al. and Boerwinkle et al. who reported associations between this polymorphism and 2-h or fasting plasma glucose levels [4,5], suggesting a potential link between this polymorphism and glucose metabolism. In addi-tion, we can not, as well, exclude the possibility that diabetes might affect the apo B signal peptide polymor-phism-related risk of CAD.
Contrary to the study of Gardemann et al. [9], we did not find any difference in the apo B allele frequencies between patients with and without MI history (65.2% for the Ins, 34.8% for the Del alleles-148 Ins/Ins, 159 Ins/Del, 42 Del/Del in patients with MI history, and 66.6% for the Ins, 33.4% for the Del alleles-72 Ins/Ins, 77 Ins/Del, 17 Del/Del in patients without MI history, NS, Fisher’s exact test).
In conclusion, our findings show that the apo B Ins/Del polymorphism affects plasma lipoprotein and apolipoprotein levels in male CAD patients and that the Ins allele is associated with the type 2 diabetes mellitus in these patients with a marginal significance.
Acknowledgements
This study was supported by project no. VS96-097 ‘Promotion of Research in Universities’ and no. CEZJ07/98: 141100002 from the Ministry of Education,
Letter to the Editor
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Youth and Physical Training of the Czech Republic and was approved by the Committee for Ethics of Medical Experiments on Human Subjects, Medical Faculty, Masaryk University, Brno.
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Petr Benesˇa,
Jan Muzˇı´ka,
Jaroslav Benedı´kb
, Lubomı´r Elblc
, Vladimı´ra Znojila
, Jirˇı´ Va´chaa aDepartment of Pathological Physiology,
Faculty of Medicine, Masaryk Uni6ersity, Kamenice3, 62500 Brno, Czech Republic E-mail: pbenes@med.muni.cz
bCenter of Cardio6ascular Surgery and Transplantation,
Brno, Czech Republic
c
Department of Cardiopulmonary Testing, Uni6ersity Hospital Brno-Bohunice, Brno, Czech Republic
