Abstract
Purpose :
The pathogenesis of Ocular mucous membrane pemphigoid (OcMMP) traditionally considering as systemic autoimmune dysregulation leading to chronic inflammation at affected sites such as ocular membrane. New evidence suggests this dysregulation inflammation may be related to gene mutation. In order to investigate the suspicion risk genes in OcMMP and how of them affecting the dysregulation biological process involved into the pathogenesis of OcMMP, we conducted a case-control gene sequencing study in MMP British cohort.
Methods :
Based on our previous genome-wide association studies (GWAS), we selected twelve risk single nucleotide polymorphisms (SNP’s) out of 6 potential genes. Then we performed SNP Genotyping Analysis by using TaqMan® SNP Genotyping Assay in 100 MMP patients and 200 healthy controls. Gene expression and cytokine production were quantified by real-time PCR and Enzyme Linked Immunosorbent Assay (ELISA), respectively.
Results :
The significant increased C allele in gene GALC/rs17203398 showed high risk with the development of MMP (p= 0,0085, OR= 0,5603). Furthermore, the significant higher frequencies of the CC genotype for GALC/rs17203398 (P=0.0149, OR = 0.3669), and the CC genotype for CASC16-CHD9/ rs9936045(p= 0,0033,OR=2.616) were found in patients with MMP. Functional experiments demonstrated that the classical pro-inflammatory cytokines IL-17A production in the supernatant of PBMC which isolated from MMP patients with CASC16-CHD9/rs9936045CC increased significantly. While the traditional anti-inflammatory factor IL-10 production was lowered in rs9936045CC genotype carriers as compared with other genotype carriers in patient with MMP.
Conclusions :
For the first time, from the gene level to function level, our results showed the essential role of gene GALC and CASC16-CHD9 in the pathogenesis of MMP. We not only confirmed the association of GALC and CASC16-CHD9 with MMP, but also identified 2 susceptibility single nucleotide polymorphisms in GALC and CASC16-CHD9 (rs17203398 and rs9936045) with MMP in British cohort.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.