Abstracts

Human Genome Diversity

Introduction. Numerous researches attempted to demonstrate the association of the insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene with cardiovascular diseases. However, large scale studies and several meta-analyses did not confirm suggested relationship. Analysis of age changes of genotypes and alleles frequencies of ACE gene in general population provides the direct estimate of their relative contribution to total mortality. It was demonstrated that ACE gene polymorphism is characterized by high interpopulation variability of genotypes and alleles frequencies in different geographical regions and ethnic groups. There are also some indications that particular genotypes may be subjected to age selection. The aim of the present study was to analyze the ACE gene insertion/deletion polymorphism in urban population of West Siberia and in a sample of West Siberian long-livers. Relatively large sample size also allowed to evaluate the changes in genotypes and alleles frequencies in consecutive middle age population groups. Material and methods The population sample have been examined in frame of WHO MONICA project (Monitoring of Determinants and Trends in Cardiovascular Diseases). (800 men and 800 woman, age 25 – 64 years old, 200 in each consecutive age decade). The ACE gene genotypes were determined for 603 men and 342 women. The long-livers were recruited in Novosibirsk at their homes or in hospices. All studied long-levers and the majority of participants from general population were of Caucasian origin. The sample of long-livers included 14 men and 53 women in age 90 – 105 years (the mean age 92.9 ± 2.8). Results The frequencies of II, ID and DD genotypes in male MONICA population were 22%, 52% and 26%, respectively (the D allele frequency - 52%). Similar data were obtained for female population. The observed frequency of D allele of ACE gene in West Siberian Caucasians is similar to that reported for majority of West European populations. The comparison of four consecutive ten-years age groups of MONICA population did not reveal significant changes in genotypes frequencies (X2 = 5.706, p = 0.457). However, frequency of DD genotype alone was significantly higher in men older then 50 years comparatively to younger age group (X2 = 5.091, p = 0.024). These data do not confirm the basic concept that D allele of ACE gene is associated with fatal diseases significantly contributing to total mortality in studied population at middle age. Contrary to general population the decrease of D allele frequency was observed in long-levers, particularly in men. The obtained data demonstrate that ACE gene insertion/deletion genotypes frequencies may change with age and may differently contribute to total population mortality in different age periods. This work was supported by RFBR grants № 99-04-49727 and № 01-04-06067

Note. Abstracts are published in author's edition

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