Analysis of the distribution of some genetic markers associated with the middle and old age multifactor pathology in the Russian population

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Abstract

We have analysed the polymorphic alleles of 19 genes in 436 patients under an outpatient preventive therapeutic screening. Eleven of the investigated genes (АРОСЗ, LPA, APOE, PON1, ACE, AGT, F5, F7, F2, PAH, and MTHFR) were associated with cardiovascular pathology, six (GSTM1, LMYC1, P53, CYP17, CYP19, and AR) - with cancer and one (DRD) - with pathologic inclinations. The average incidences of the genotypes and alleles were comparable with the typical values of other European populations. Significant correlation has been registered between the distributions of the analysed alleles for the certain gene pairs.

There was two-fold decrease in the incidence of the combination of l/l mutated genotype of the ACE gene, that is associated with an increased insulin-resistance risk, with an mutated allele of the MTHFR gene, that is associated with higher blood plasma homocysteine concentration. There were no genotypic classes, in which 4G homozygous mutation in the PAH gene, that is associated with disturbed fibrinolysis, was combined with mutations in the the F5 and F2 genes, that are associated with blood coagulation system activation. At the same time, significantly increased incidences were revealed for the genotypes, in which homozygous deletion in the GSTM1 gene, that absolutely eliminates glutathione-S-transferase p-1 activity (one of the detoxication system enzymes), was combined with a pathologic mutation in the MTHFR gene, or with 4G/4G homozygous mutations of the PAH gene. Various age groups were significantly different in the distribution of certain genetic markers. The incidences of polymorphic alleles of the APOC3, APOE, MTHFR, and DRD genes were decreased with age, while the incidences of F2, F5, and РАН alleles were surprisingly increased. Consequently, the interpretation of genetic risk factors must include the analysis of population characteristics, genetic interactions, and age-related changes in the distribution of polymorphic alleles.

About the authors

V. K. Khavinson

St. Petersburg Institute of Bioregulation and Gerontology

Email: shabanov@mail.rcom.ru

член-корреспондент РАМН

Russian Federation, St. Petersburg

D. V. Solovieva

St. Petersburg Institute of Bioregulation and Gerontology

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

D. L. Strekalov

St. Petersburg Institute of Bioregulation and Gerontology

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

E. N. Imyanitov

St. Petersburg Institute of Bioregulation and Gerontology

Author for correspondence.
Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

A. A. Lyschev

St. Petersburg Institute of Bioregulation and Gerontology

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

V. N. Gorbunova

St. Petersburg Institute of Bioregulation and Gerontology

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

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