Associations of Polymorphisms of NOD2/CARD15, CRP and FTO Genes with Cardiovascular Risk Factors, Damages to Target Organs and Cardiovascular Diseases in Patients with Ulcerative Colitis and Crohn’s Disease

Abstract

INTRODUCTION: The role of genetic factors in the development of cardiovascular diseases (CVD) in patients with inflammatory bowel diseases (IBD) is practically unknown.

AIM: To study the frequency of carriage of allelic polymorphous variants of NOD2/CARD15 (3020insC rs5743293, Gly908Arg rs2066845), CRP (+1444C>T rs1130864), FTO (A23525T rs9939609) genes and to perform a comprehensive assessment of damage to the target organs, diastolic myocardial dysfunction of the left ventricle and CVD in patients with ulcerative colitis and Crohn’s disease living in the Ryazan District.

MATERIALS AND METHODS: The study involved 62 patients (41 (66%) women, 40.5 [33.5; 52.25] years old) with IBD (51 patients with ulcerative colitis, 11 patients with Crohn’s disease) in whom 3020insC and Gly908Arg polymorphisms in CARD15 (NOD2) gene, C1444T in CRP gene and А23525Т in FTO gene were determined using allele-specific polymerase chain reaction. After that, the frequency of carriage of their allelic variants and association with CVRFs, damage to the target organs (through evaluation of the arterial stiffness, pulse pressure, hypertrophy of the left ventricular myocardium, ankle-brachial index) and CVDs was evaluated.

RESULTS: According to the aims of the study, the frequency of carriage of allelic polymorphic variants of genes was determined: 3020insC in gene CARD15 (NOD2) rs5743293 85.5% — homozygote for allele 1, 14,5% — heterozygote; Gly908Arg in gene CARD15 (NOD2) rs2066845 93.5% — homozygote for allele 1, 6.5% — heterozygote; C1444T in gene CRP rs1130864 50% — homozygote for allele 1, 41.9% — heterozygote, 8.1% — homozygote for allele 2; А23525Т in gene FTO rs9939609 38.7% — homozygote for allele 1, 38.7% — heterozygote, 22.6% — homozygote for allele 2. The prevalence of arterial hypertension was 31%, of obesity by body mass index — 18%, by waist circumference — 29%, and of dyslipidemia — 53%. Statistically significant associations were found between: 1) hypercholesterolemia and Gly908Arg polymorphism in gene CARD15 (NOD2) rs2066845 (÷2 = 6.005; p = 0.014), 2) family history of early CVD and 3020insC polymorphism in gene CARD15 (NOD2) rs2066845 (÷2 = 4.561; p = 0.033), 3) arterial hypertension and 3020insC polymorphism in genеCARD15 (NOD2) rs5743293 (÷2 = 4.65; p = 0.031).

CONCLUSION: The prevalence of arterial hypertension, obesity and dyslipidemia in patients with IBD is considerably lower in the given study than in the individuals of comparable age in the epidemiological MERIDIAN-RO study conducted in the Ryazan region. Statistically significant associations were found between the studied polymorphisms and hypercholesterolemia, family history of early cardiovascular diseases and arterial hypertension.

Keywords

3020insC / Gly908Arg / C1444T / A23525T / inflammatory bowel diseases / arterial stiffness / cardio-ankle vascular index

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