Carotid intima-media thickness in patients with arterial hypertension among the population of Gornaya Shoriya: relationship with genetic factors

Abstract

Purpose. We aimed to identify the associations of polymorphisms of ACE, AGT, AGTR1, ADRB1, ADRA2B, MTHFR and N0S3 candidate genes with the increased carotid intima-media thickness (CIMT) in patients with arterial hypertension (AH) among indigenous (the Shors) and non-indigenous population of Gornaya Shoriya. Material and methods. We performed a clinical and epidemiological study of the compactly settled papulation in the remote areas of Gornaya Shoria. This region of middle mountains is situated in the south of Western Siberia. We examined 830 subjects [494 subjects - the representatives of indigenous nationality (the Shors), 336 subjects - representatives of non-indigenous nationality (90% among them were the representatives of the European ethnicity)]. AH was diagnosed according to the 'National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010). The thickness of carotid intima-media in patients with AH was evaluated using ultrasound duplex scanning at Medison Sonoace PICO apparatus (235 subjects among the Shors and 178 subjects among the non-indigenous inhabitants). Polymorphisms of genes ACE (I/D, rs 4340), AGT (c.803T> C, rs699), AGTR1 (A1166C, rs5186), ADKB1 (c.145A>G, Ser49Gly rs1801252), ADRA2B (I/D, rs 28365031), MTHFR (c.677C> T, Ala222Val, rs1801133) andNOS3 (VNTR, 4b/4a) were tested using PCR. Results. Thefrequency of the increased CIMT in patients with AH was higher in the indigenous ethnic group (78.3%) as compared with the non-indigenous group (69.7%, p = 0.046). A correlation analysis revealed a direct correlation between the levels of systolic and diastolic blood pressure and CIMT (r- 0.4, p - 0.0001 and r= 0.3, p = 0.0001 among the Shors; r-0.3,p - 0.0001 and r-0.2,p - 0.0001 among the non-indigenous population, respectively). In the group of the examined subjects with AH and carotid atherosclerosis the frequency of homozygous I/I genotype of ACE gene in the cohort of the Shors was higher, and the frequency of heterozygous I/D genotype, on the contrary, was lower than in the cohort of non-indigenous representatives. In the group of subjects with the indicated pathology the percentage of the carriers of the prognostically favourable I/1 genotype of ADRA2B gene among the Shors was lower than among the subjects of non-indigenous ethnos. The similar pattern was also revealed regarding to the prevalence of mutant Т/ T genotypes of MTHFR gene and 4a/4a of NOS3 gene. Conclusion. The association of T/C genotype of AGT gene and C/T genotype of MTHFR gene in a superdominant mode of inheritance with carotid atherosclerosis was established in the cohort of the Shors. The risk effect of C/T genotype of MTHFR gene was increasing in female subjects aged 18-64 years and having dyslipidemia. The protective effect was revealedfor ADKB1 gene in log-addictive mode of inheritance. In the cohort ™ of non-indigenous ethnos AGT gene in log-addictive mode of inheritance was associated with carotid atherosclerosis. - The protective effect was established for I/ D genotype of ADRA2B gene in a superdominant mode of inheritance.