Clinicalgenetic determinants of albuminury development among patients with arterial hypertension.

Abstract

Purpose. To establish the associations of polymorphisms of АСЕ, AGT, AGTR1, ADR81, ADRA2B, MTHFR and NOS3 candidate genes with microalbuminuria in patients with arterial hypertension (AH) among indigenous (the shors) and non-indigenous population of Mountain Shoria. Material and methods. A clinical and epidemiological study of the compactly settled population in the remote areas ofMountain Shoria was conducted. This region of middle mountains is located in the south of Western Siberia. 1409persons [901 subjects - the representatives of indigenous nationality (the shors), 508 subjects - representatives of non-indigenous nationality (90% among them were the representatives of the European ethnicity)] were examined. AH was diagnosed according to the National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010). Photometric method was used to study the urine albumin level. The albuminuria index of more than 30 mg/day was taken as elevated. Polymorphisms of genes ACE (I/D, rs 4340), АGT (c.803T>C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A>G, Ser49Gly, rs1801252), ADRA2B (I/D, rs 28365031), MTHFR (c.6770T, Ala222Val, rs1801133) andNOS3 (VNTR, 4b/4a) were investigated using polymerase chain reaction test. Results. An increase of the chances of microalbuminuria frequency development in patients with 3rd grade AH and duration of anamnesis of this disease for more than 10 years in both ethnic groups was established. In cohort of shor people the elevated level of albuminuria was interrelated with hypertriglyceridemia (OR 2.86), hypoalphacholesterolemia (OR 5.57) and hyperbetacholesterolemia (OR 2.49). The ACE gene was associated with a high risk of microalbuminuria (OR 2.05) in the log-additive type of inheritance, the D/D genotype of the ADRA2B gene (OR 6.00) - according to the recessive type of inheritance. At division of the examined population of shors according to age sign the relationship of heterozygous C/T genotype of MTHFR gene with the appearance of microaluminuria in persons of the age group of 18-64 years was established (OR 3.25). In the cohort of the non-indigenous ethnos the increased albuminuria level was influenced by obesity (OR 2.72), including abdominal (OR 3.14). Minor genotype C/C of the AGTR1 gene was associated with this target organ damage (OR 8.66) according to the recessive type of inheritance, the prognostically adverse genotype D / D of the ADRA2B gene (OR 6.53) - by the dominant type. The genotype T/T of the MTHFR gene was also proved to be interrelated with the microalbuminuria (OR 7.16) by the recessive type of inheritance. Conclusion. The determination of polymorphisms of AH candidate genes and the detection of associations with microalbuminuria expands understanding the concept of the genetic component of the cardiorenal continuum and creates the prerequisites for the development of a more advanced and effective prevention program.