Abstract

Objective. To study the frequency distribution of genotypes and alleles of polymorphic loci of folate cycle genes ( MTHFR C677T, MTHFR A1298G, MTR A2756G, MTRR A66G) in patients with gout and to evaluate their association with the risk of the disease. Material and Methods. 80 patients (69 men and 11 women) with gout were examined. The diagnosis of gout was made according to the classification criteria ACR/EULAR, 2015. DNA isolated from white blood cells of whole peripheral blood was the material used in the genetic analyses. All patients were genotyped to detect polymorphisms of the MTHFR C677T, MTHFR A1298G, MTR A2756G, MTRR A66G gene loci. Statistical data processing was performed using the software package Statistiсa 10.0. Results. Genetic polymorphisms of the MTHFR C677T and MTR A2756G genes are involved in the development of gout in individuals of Russian ethnicity in the population of the Trans-Baikal Territory. Minor T allele (χ 2 = 4.65, p = 0.03, OR = 1.83, CI95% = 1.05–3.17) and the T/T genotype (χ 2 = 6.5, p = 0.01, OR = 5.94, CI95% = 1.3–27.00) of the C677T locus of the MTHFR gene, minor G allele (χ 2 = 6.46, p = 0.01, OR = 2.38, CI95% = 1.2–4.69) and the A/G genotype of the MTR A2756G gene (χ 2 = 5.78, p = 0.01, OR = 2.66, CI95% = 1.18–5.98 ) were identified as alleles and genotypes having increased risk for developing gout. While the C allele (χ 2 = 4.65, p = 0.03, OR = 0.55, CI95% = 0.31–0.94) of the MTHFR C677T gene, and allele A (χ 2 = 6.46, p = 0.01, OR = 0.42, CI95% = 0.21–0.83) and genotype A/A (χ 2 = 7.58, p = 0.006, OR = 0.33, CI95% = 0.15–0.74) of the A2756G locus of the MTR gene were determined as genotypes and alleles having a protective effect. Conclusion. Significant differences were found in the frequency distribution of genotypes and alleles of the MTHFR C677T and MTR A2756G genes in gout patients compared with the control group. The presence of minor T allele and the T/T genotype of MTHFR C677T gene, the minor G allele and the A/G genotype of MTR A2756G gene was associated with an increased risk of gout. In contrast, the carriage of the C allele of MTHFR C677T gene, allele A and the genotype A/A of MTR A2756G gene had a potentially protective effect.

Highlights

  • Note: UA – uric acid; p – the level of statistically significant differences compared with the control group

  • Все пациенты были генотипированы для выявления полиморфизмов генов фолатного цикла (4 мутации) – Methylenetetrahydrofolate reductase (MTHFR) С677T, MTHFR А1298G, MTR А2756G, MTRR А66G с использованием набора «Генетика метаболизма фолатов» (ООО НПО «ДНК-Технология», Россия) методом полимеразной цепной реакции с детекцией продукта амплификации в режиме реального времени

  • Note: p – the level of statistically significant differences less than 0.05 indicates deviations in the frequency distribution of genotypes according to Hardy-Weinberg equilibrium; χ2 - χ2 test

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Summary

Материал и методы

В исследование включены 80 мужчин и женщин с подагрой, находившихся на лечении в ЧУЗ «Клиническая больница» «РЖД-медицина» Медиана возраста пациентов составила 54,0 [45,0; 65,0] года (мужчин – 53,0 [41,5; 66,2], женщин – 55,6 [45,2; 67,0]). Диагноз подагры выставлен согласно классификационным критериям ACR/ EULAR, 2015 [18]. В таблице 1 представлена клиническая характеристика исследуемых групп. У половины пациентов подагра дебютировала в возрасте от 40 до лет, у 35% – в возрасте старше лет (35,2%), каждый пятый резидент испытал первый приступ заболевания в возрасте моложе 40 лет. Более половины (52,6%) пациентов страдали подагрой от 1 до 5 лет, каждый четвертый (25,4%) – от 6 до 10 лет, 22% имели анамнез заболевания более 10 лет. Характеристика больных подагрой в зависимости от характера течения заболевания представлена в таблице 2. Среди пациентов 57,5% имели рецидивирующее, 42,5% – хроническое течение подагры.

Контрольная группа Control group
Характер течения подагры Gout course
Ожидаемая Expected
Frequency distribution of the genotypes
Всего Totally
Информация о вкладе авторов
Information on author contributions
Findings
Information about the authors
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