FAS promoter polymorphisms and serum sFas level are associated with increased risk of nerve damage in Bangladeshi patients with Guillain-Barré syndrome

Abstract

Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system triggered by molecular mimicry between pathogen lipopolysaccharides and host nerve gangliosides. Polymorphisms in the Fas receptor (FAS) and Fas ligand (FASL) genes may potentially alter the elimination of autoreactive immune cells and affect disease susceptibility or disease severity in GBS. We detected single nucleotide polymorphisms (SNPs) in FAS (-1377G/A and -670A/G) and FASL (-843C/T) in a prospective cohort of 300 patients with GBS and 300 healthy controls from the Bangladeshi population. Genotype distributions were not significantly different between patients with GBS and healthy controls. The FAS -670 AG heterozygous (P = 0.0005, OR = 2.5, 95% CI = 1.5–4.2) and GG homozygous (P = 0.0048, OR = 2.6, 95% CI = 1.3–5.0) genotypes were more common in patients with anti-GM1 antibodies than patients without anti-GM1 antibodies. The FAS -670 G allele was more prevalent in anti-GM1 antibody-positive than -negative patients (P = 0.0002, OR = 1.9, 95% CI = 1.4–2.7) and also in patients with the axonal subtype than demyelinating subtype (P < 0.0001, OR = 4.8, 95% CI = 2.3–10.1). The 1377G/-670G GG haplotype was significantly associated with the axonal subtype (P < 0.0001) and anti-ganglioside antibody-positivity (P = 0.0008) in GBS. Serum sFas (237.5 pg/mL vs. 159.5 pg/mL; P < 0.0001) and sFasL (225.1 pg/mL vs. 183.4 pg/mL; P = 0.0069) were elevated in patients with GBS compared to healthy controls, and among patients with high serum sFas was associated with severe GBS (P = 0.0406). In conclusion, this study indicates FAS-FASL promoter SNPs may promote the production of cross-reactive anti-ganglioside antibodies in GBS.

Investigation of the Relation Between FAS, FASLG Polymorphisms and Serum Fas, FasL Levels in Patients with Psoriasis

“…In a study of systemic lupus erythematosus (SLE) patients in order to understand the role of the Fas/FasL system in autoimmune diseases, when the levels of Fas and FasL proteins in SLE patients were found to be increased due to the severity of the disease, there was an inverse correlation between sFas levels and the stages of the disease (25). Also, in another study investigating the effects of FAS and FASLG promoter region polymorphisms on serum levels in Guillain-Barré syndrome (GBS) patients, it was reported that promoter region SNPs raised serum levels and could be associated with the disease (26). In our study, we observed that sFas and sFasL levels significantly increased in patients compared to the control group (p<0.001), which was similar to the studies mentioned above.…”

Guillain–Barré syndrome in low-income and middle-income countries: challenges and prospects

“…One factor that determines this low risk is the requirement for carbohydrate mimicry (which is not present in all C. jejuni strains) to develop the cross-reactive antibody response to gangliosides that evolves into GBS 2 , 3 , 10 . However, genetic and nutritional factors might also influence the patient’s susceptibility to producing such antibodies 82 – 84 . Poor nutritional status, and specifically malnutrition, alters the dysfunctional immune responses implicated in the pathogenesis of various autoimmune diseases 85 .…”

“…Immune response activation following an infection has also been associated with genetic polymorphisms. Several studies have found associations between GBS and polymorphisms in the TNF gene (which encodes tumour necrosis factor) and the MBL2 gene (which encodes mannose-binding protein C) 2 , 82 – 84 .…”

The Peculiarities of Immune Regulation and the Polymorphic Variants of Candidate Genes Associated With Them in Oil Production Workers With Vegetative Regulation Disorders

“…According to the available literature data, the predominance of the C-allele of the wild-type FAS gene is associated with an increase in the expression level of the membrane receptor of lymphocytes, but the surveyed population is characterized by only a slight increase in the content of CD3+CD95+ lymphocytes. At the same time, the level of CD3+CD95+ lymphocytes is statistically significantly (p < 0.05) decreased relative to the reference level, regardless of the presence of violations of autonomic regulation of physiological functions of the body in oil workers, which indicates the suppression of apoptotic processes in the examined individuals [11,12].…”

“…The gene pool of the observation group is distinguished by an increased frequency of the variant Aallele of the cytochrome P450 gene CYP2C19*2 (rs4244285) due to an increase in the proportion of variant homozygotes and heterozygotes for this gene in the surveyed sample (OR = 2.69; CI: 1.05-8.45). According to the literature, the replacement of G681A in the CYP2C19 gene determines the expression of an enzyme with low activity and a decrease in the metabolic rate of xenobiotics and drugs in carriers of the variant genotype [12]. The polymorphism of the gene for the regulator of apoptosis FAS (rs1159120) is characterized by a significant (p < 0.05) increase in the frequency of the Callele of the wild type due to the significant prevalence of wild-type homozygotes in the group of oil production workers with disorders of autonomic regulation relative to the comparison group.…”