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Interleukin-37 gene polymorphism and susceptibility to coronavirus disease 19 among Iraqi patients

ABSTRACT: Coronavirus disease 19 (COVID-19) is a highly contagious respiratory viral infection. Dysregulated immune response is an important feature of disease, and cytokines are among the most important mediators of dysregulated immunity. Interleukin-37 (IL-37) is one such cytokine and studies have indicated its role in pathogenesis of COVID-19. However, IL37 gene polymorphisms have not been identified in patients with COVID-19. Therefore, this case-control study (100 patients and 100 controls) was performed to understand the role six single nucleotide polymorphisms of IL37 gene (SNPs: rs3811042, rs3811043, rs2466449, rs3811045, rs3811046 and rs3811047) in susceptibility to COVID-19 among cases with severe disease. These polymorphisms were identified by Sanger DNA sequencing. Results revealed that TG genotype of rs3811046 showed a significantly increased frequency in patients compared to controls (61.0 vs. 38.0%; odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.45–4.50; probability [p] = 0.002; corrected p [pc] = 0.01). GA genotype of rs3811047 also showed an increased frequency in patients but the pc-value was not significant (39.0 vs. 24.0%; OR = 2.02; 95% CI = 1.10–3.71; p = 0.033; pc = 0.165). Haplotype analysis revealed a significantly increased frequency of the haplotype G-C-A-T-T-A (in the order: rs3811042, rs3811043, rs2466449, rs3811045, rs3811046 and rs3811047) in COVID-19 patients compared to controls (0.055 vs. 0.006; OR = 10.23; 95% CI = 1.53–68.14; p = 0.003; pc = 0.03). In conclusion, the study indicated that two variants of IL37 gene (rs3811046 and rs3811047) may be associated with susceptibility to COVID-19 among Iraqi population.

SUBMITTER: Ahmed A

PROVIDER: S-EPMC8553418 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe low-density lipoprotein receptor (LDLR) plays a significant role in maintaining the cellular cholesterol homeostasis. Mutations in the LDLR gene can lead to a significant rise in plasma LDL levels that may result in an increased risk of atherosclerosis and coronary heart disease. The purpose of this study was to assess the potential association of the LDLR rs688 polymorphism with cardiovascular disease (CVD) in patients with end-stage kidney disease (ESKD) undergoing hemodialysis.MethodsIn this case-control study the polymorphism was genotyped by the allele specific PCR method in 800 patients with ESKD and 500 healthy controls. The genotype and allele distribution was compared in subgroups of patients with CVD (552) versus those without CVD (248).ResultsA significant difference was observed in genotype distribution among ESKD patients and healthy controls. The frequencies of the T allele and TT genotype in ESKD group were significantly higher, with OR (95% CI) 2.2 (1.87-2.6), p < 0.0001 and 5.84 (3.94-8.65), p < 0.0001, respectively. In the he ESKD cohort the distribution of the rs688 was compared between CVD+ and CVD- subgroups. A strong association of the polymorphism with the CVD risk was observed in this analysis. The frequencies of the T allele and TT genotype were significantly higher in CVD+ subgroup, with OR (95% CI) 3.4 (2.71-4.26), p < 0.0001 and 13.2 (7.87-22.09), p < 0.0001, respectively. A multivariate logistic regression analysis was performed to estimate the association between rs688 T variant and risk of CVD. After adjustment for age, sex, BMI, hypertension and diabetes, both CT and TT genotypes were associated with an increased risk of developing CVD in the dominant, recessive and codominant models of inheritance. No significant differences in serum LDL cholesterol levels were found when compared between genotypes.ConclusionsThe present study is the first to demonstrate the association of the LDLR gene polymorphism with increased susceptibility to cardiovascular disease in ESKD patients. This finding needs further investigation to confirm that LDLR rs688 might be a novel genetic risk factor with some prognostic capacity for CVD in ESKD patients.

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Interleukin-37 gene polymorphism and susceptibility to coronavirus disease 19 among Iraqi patients

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