We have analyzed the frequency of polymorphisms for Met235Thr and Thr174Met gene AGT, Leu 28 Pro gene APOE, C786T gene NOS3, Glin192Arg gene PON1 and Lys198Asn gene EDN1. Total 218 people were examined. Selection was based on the family principle including 27 persons of age group 60 > (I generation of persons exposed to direct radiation), 141 their children (II generation) and 50 grandchildren (III generation). It is known that ethnic differences are important in the inheritance of some genotypes which may play a role in the predisposition to certain diseases. Therefore, a comparative analysis was conducted separately for Kazakh and Russian people. 140 males and 296 females; 161 Kazakhs and 57 Russian were included to our study (table 1).
Table 1 – Sex and ethnic characteristics of the people examined for genetic predisposing to cardiovascular diseases
Kazakhs
Russians
Total
I generation
Offspring (generations)
I generation
Offspring (generations)
I generation
Offspring (generations)
II
III
II
III
II
III
Males
Females
Results
The frequency of heterozygous type of inheritance for genotype AGT Thr174Met in the Kazakh people was 50.31 %, while in the people of Russian nationality this type of inheritance was only 32.47 % (p <0.01). The frequency of the homozygous mutant allele Met235Thr in the people of Russian nationality was almost ten times higher in Kazakhs ethnic group. Heterozygous and homozygous mutant genotypes APOE Leu28Pro in the Russian occurred significantly more frequently than in the Kazakh population (figure 1).
Figure 1 – AGT Thr174Met and Met235Thr genotypes frequency depending on nationality, %
In both ethnic groups there was a high percentage of heterozygous alleles PON1, more pronounced in the group of Kazakh nationality (47.65 and 40.0%, respectively). The frequency of homozygous mutant alleles had no differences in ethnic groups (figure 2).
Figure 2 – Glin192Arg genotype PON1 and Leu 28 Pro genotypes APOE frequency depending on nationality, %
For gene EDN1 we can note the high percentage of heterozygous allele Lys198Asn, which indicates a high probability of endothelial dysfunction in both ethnic groups. Homozygous mutant alleles occurred among the Kazakhs in 3.36% of cases, among Russian - in 4.44%. Approximately the same situation was observed in the frequency of heterozygous allele NOS3 C786T (figure 3).
Figure 3 – C786T genotype NOS3 and Lys198Asn genotypes EDN1 frequency depending on nationality, %
It was found high frequency of heterozygous type inheritance for Thr174Met polymorphisms gene AGT (46.15 %; 48.9 %, and 52.0 % respectively in I, II, and III generations); for people of I, and III generations heterozygous type prevailed over homozygous. Monozygotic pathological type of allele was higher in the older persons exposed to direct irradiation (3.85% compared with 1.42% in the people of II generation and 2.00% in the people of III generation (p <0.05; 0.05). For Met235Thr frequency of heterozygous type in the offspring of exposed people was higher compared with I generation (48.15; 51.2 %, and 54.0 % respectively in I, II, and III generations (p<0.05; 0.05)) (figure 4).
Figure 4 - AGT Thr174Met and Met235Thr genotypes frequency in the groups of radiation risk, %
Heterozygous type inheritance for APOE Leu28Pro was dominant in the II and III generations (51.64 % and 50.0 % respectively; 19.23 % in I generation (р<0.05; 0.05). Homozygous mutant type inheritance for PON1 Gln192Arg in the offspring of III generation (age <30) was 8.33 % versus 1.64 % in II generation (p<0.01; 0.01) (figure 5).
Figure 5 –APOE Leu28Pro and PON1 Gln192Arg genotypes frequency in the groups of radiation risk, %
It was found unexpected high frequency of monozygotic pathological mutations for NOS3 C786T genotype in the people of I and III generation (26.1 % and 20.83 % respectively). This type of inheritance requires further investigation for determining the possibility of radiation induction of this effect. Frequency of heterozygous type inheritance for genotype EDN1 Lys198Asn was 36.0 %, 38.62 %, and 39.58 % respectively. It indicates a high risk of development of endothelial dysfunction in the young people (figure 6).
Figure 6 –NOS3 C786T and EDN1 Lys198Asn genotypes frequency in the groups of radiation risk, %
