Variants of the vitamin D receptor gene and the expression of microRNA‑21, microRNA‑125a, microRNA‑125b and microRNA‑214 in coronary heart disease

Background . The protective effects of vitamin D in relation to atherogenesis are realized by vitamin D receptors (VDR). Variants rs10735810, rs731236, rs1544410 and rs797532 of the VDR gene are involved in regulating the stability of its mRNA. МicroRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21 bind to the 3’regulatory domain of the VDR gene and affect VDR protein expression. Оbjective . To evaluate the expression levels of microRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21 in coronary heart disease (CHD) patients with rs10735810, rs731236, rs1544410 and rs797532 variants of the VDR gene. Design and methods . The genotypes of the VDR gene were determined in 766 CHD patients and in 336 people without CHD (comparison group) by polymerase chain reaction (PCR) followed by restriction analysis. MicroRNA expression was determined by real-time PCR. Results . The ff, Ff genotypes and the f allele of the VDR gene (rs10735810) were more often detected in CHD patients than in the comparison group (p = 0,001, p = 0,03 and p = 0,047, respectively). Carriage of the ff (rs10735810) genotype of the VDR gene was associated with an increased risk of CHD (odds ratio (OR) = 1,80; 95 % confidence interval (CI): 1,30–2,50, p = 0,0004). The aa genotype of the VDR gene (rs797532) and the bb genotype of the VDR gene (rs1544410) were more common in CHD patients than in the comparison group (p = 0,008 and p = 0,001). The presence of the aa and bb genotypes of the VDR gene was associated with an increased risk of CHD (OR = 1,50; 95 % CI: 1,11÷2,02, p = 0,008, OR = 1,77; 95 % CI: 1,35÷2,32, p = 0,001, respectively). The expression levels of microRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21 in the blood are higher in CHD patients than in the control group (p < 0,001). The expression of microRNA‑125a was higher in smoking patients than in non-smokers (59,85 (21,69; 73,06) conventional units of expression (UE) and 32,00 (4,59; 67,85) UE, respectively; p = 0,04). In CHD patients with Tt genotype of the VDR gene (rs731236), the expression of microRNA‑214 is higher than in carriers of the tt genotype of the VDR gene (p = 0,03). In CHD patients with the aa genotype of the VDR gene (rs797532), the expression of microRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21 in the blood is higher than in patients with the AA genotype of the VDR gene (p < 0,05). The expression of microRNA‑125a, microRNA‑125b and microRNA‑21 in the blood of CHD patients, carriers of the bb genotype of the VDR gene (rs1544410), is higher than in those with the BB genotype of the VDR gene (p < 0,05). Conclusion. MicroRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21, genotypes aa, ff and bb of the VDR gene (rs797532, rs10735810, and rs1544410 variants), represent promising markers of CHD. Variants of the VDR gene can affect the expression levels of microRNA‑214, microRNA‑125a, microRNA‑125b and microRNA‑21.