Abstract
(1) Background: interleukin 23 (IL-23) and interleukin 27 (IL-27) modulate the activity of T helper 17 cells (Th17) with critical roles in autoimmune diseases and multiple sclerosis (MS). The genes responsible for cytokine generation are highly influenced by the presence of single nucleotide polymorphisms (SNP) in main regions such as regulatory sequences or in promoter regions, contributing to disease susceptibility and evolution. The present study analyzed the associations of IL-23 and IL-27 SNPs with susceptibility to multiple sclerosis. (2) Methods: We performed a case-control study including 252 subjects: 157 patients diagnosed with MS and 95 controls. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypes for IL-27 T4730C (rs 181206), IL-27 A964G (rs 153109), and IL-23 receptor gene (IL-23R) G1142A (rs 11209026). (3) Results: The IL27-T4730C gene polymorphism was significantly associated with an increased odds of MS under the dominant genetic model (TC + CC variant genotypes, adjusted odds ratio OR = 4.06, 95% CI: 2.14–7.83, p-value = 0.000007, Q-value = 0.000063). Individuals carrying the IL-27 A924G variant (AG + GG) genotype presented higher odds of MS compared to non-carriers under the dominant model (adjusted OR = 1.93, 95% CI: 1.05–3.51, p-value = 0.0324, Q-value = 0.05832) and the allelic genetic model (unadjusted p-value = 0.015, OR = 1.58, 95% CI: 1.09–2.28), while IL-23-R381Q SNP conferred a decreased odds of MS under a codominant model of inheritance (adjusted OR = 0.26, 95% CI: 0.08–0.92, p-value = 0.0276, Q-value = 0.058) and an allelic model (unadjusted p-value = 0.008, OR = 0.23, 95% CI: 0.07–0.75). In an additive model with adjustment for age group (≤40 years vs. >40 years), sex and smoking, patients carrying the G-C (A964G, T4730C) haplotype had a 3.18 increased risk (95% CI: 1.74–5.81, p < 0.001) to develop multiple sclerosis. (4) Conclusions: The results of the current study showed a significant relationship of IL-27-A964G and IL-27-T4730C polymorphisms with increased risk of MS, and also the protective role of the IL-23-R381Q polymorphism. Moreover, the haplotype-based analysis proposed the mutant G-C (A924G, T4730C) as a significant risk haplotype for the development of MS.
Highlights
Multiple sclerosis (MS) is the most commonly acquired demyelinating disorder of the central nervous system (CNS) in the young adult [1].The prevalence of multiple sclerosis (MS) in Western Europe is estimated at 0.1–0.2% of the population (100–200 cases per 100,000 people), leading to disability and socioeconomic burden [2]
In order to identify the genotypes for the three genetic variations, interleukin 27 (IL-27)-T4730C, IL-27A964G and interleukin 23 (IL-23)-R381Q, 2 mL of peripheral blood were collected through venipuncture in ethylenediamine tetraacetic acid (EDTA) anticoagulated tubes for both patients with multiple sclerosis and controls
This is the first study performed in the Romanian population which tried to evaluate the association between three single nucleotide polymorphisms (SNP), IL-27-T4730C, IL-27-A964G and IL-23-R381Q, and susceptibility to multiple sclerosis
Summary
The prevalence of MS in Western Europe is estimated at 0.1–0.2% of the population (100–200 cases per 100,000 people), leading to disability and socioeconomic burden [2]. Due to the increasing awareness of MS in the society and due to the available diagnostic tools, the reported prevalence is significantly increasing. The etiology of MS is determined by a complex interplay between environmental factors, genetic factors and lifestyle, leading to demyelinating lesions, axonal loss, astrocytic gliosis and microglial activation [3,4]. The environmental factors and lifestyle factors (diet, smoking and obesity) maintain a pro-inflammatory status characterized by high levels of circulating cytokines [4,8]. The persistent inflammation determines the loss of trophic support provided by myelin, impairing axonal survival and contributing to a failure of remyelination [9]
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