Polymorphisms in glucocorticoid receptor gene: a susceptibility factor to Guillain-Barré syndrome in a Bangladeshi population

Abstract

Guillain-Barre syndrome (GBS) is an autoimmune disorder in which the body's immune system attacks part of the peripheral nervous system with a greater variable clinical progression, severity, and outcome. Infectious agent as well as host factor are responsible for developing GBS. Glucocorticoids are the steroid hormones that bind with glucocorticoid receptor (GR) gene to decrement the immune reaction through down-regulating the cytokine responsible for cellular and humoral immune reaction and thus, polymorphisms in GR gene act as a factor to develop autoimmune disease. Hence, in the population of 71 patients with GBS and healthy controls of Bangladesh , five known SNPs of glucocorticoid receptor gene along with the haplotype patterns of genetic variations has been studied. The study supports to investigate the individual SNP as well as the haplotype that are related to the susceptibility of developing GBS and their role in disease outcome. During the course of this study, which includes 5 possible SNPs in the GR gene, shows 6 different haplotype frequencies. No strong evidence has been found to conclude that polymorphism in GR gene is related in developing GBS, even though, BclI (C/G), genotype shows an association with autoantibody GD1a production (p=0.024, OR, 6.94; 95% CI, 1.28-37.58). Two associations with haplotypes have been found which includes haplotype 1 in C. jejuni positive acute motor axonal neuropathy (AMAN) type patient with GBS (p=0.048, OR, 5.55; 95% CI, 1.02-30.33) and haplotype 3 with disease outcome (p=0.008, OR, 0.06; 95% CI, 0.007-0.478), which means that disease improvement rate is 94% slower in the presence of haplotype 3. Additionally, pairwise Linkage disequilibrium has been performed to find the association within this 5 locus which shows an association among N363S with BclI, N363S with GR-9beta and TthIII-1 with ER22/23EK based on D’-value and P-value.