AN INTRONIC POLYMORPHISM RS11773845 IN CAV1 GENE IS ASSOCIATED WITH THE RISK OF DEVELOPING ATRIAL FIBRILLATION IN UZBEK PATIENTS WITH ARTERIAL HYPERTENSION

Objective: To determine the relationship of the rs11773845 polymorphism of the CAV1 gene with atrial fibrillation (AF) in patients with arterial hypertension (AH) in the Uzbek population. Design and method: The study included 154 patients with paroxysmal (n=47), persistent (n=21) and permanent (n=86) forms of AF. The control group (n=91) consisted of hypertensive patients without AF. The average age of hypertensive patients with AF was 65.2±10.8 years, and control group was 63.6±10.7 years. The diagnosis of AF was based on ECG and/or Holter ECG findings using standard diagnostic criteria. Genotyping of samples for carriage of allelic variants of the rs11264280 polymorphism was carried out using the RFLP-PCR method. Relative risk (OR) was calculated using genetic models. For all analyses, p values <0.05 were considered statistically significant. Results: Among hypertensive patients with AF, genotype of the rs11773845 polymorphism of the CAV1 gene was revealed: AA genotype - determined in 55 (35.7%) patients, AC genotype - in 80 (52.0%), CC genotype - 19 (12.3%), χ 2 =54.955, p=0.000. The allelic distribution showed a predominance of carriage of the A allele: A allele – 61.7%, C allele – 38.3%, χ 2 =33.662, p=1e-8. Among controls, on the contrary, the frequency of the C allele prevailed: 68.1% and 31.9% - the frequency of the A allele, χ 2 =47.868, p=0.000. The ratio of AA:AC:CC genotypes was as follows: 16.5%: 30.8%: 52.7%, (χ 2 =27.33, p=0.000) respectively. Based on the multiplicative model of inheritance, a significant accumulation of the A allele was demonstrated among 154 hypertensive patients with AF in 61.7% (χ 2 =40.70, p=0.000; OR=3.44, 95% CI 2.34-5.07), while the C allele was less common in 38.3% of cases. The dominant model of inheritance also demonstrated the association of AA + AC genotypes with the risk of developing AF in patients with AH, so AA + AC genotypes were more common in 87.7% (χ 2 = 47.01; p = 0.000; OR = 7.93, 95% CI 4.21-14.93) than CC genotype in 12.3% of cases. Conclusions: The AA+AC genotypes and the A allele of the rs11773845 polymorphism of CAV1 gene associated with risk of developing AF in Uzbek patients with AH.

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