Autoimmunity Risk Variants in the PTPN22 and CTLA4 Genes are Associated with Infectious Onset of ME/CFS

Project description

Single nucleotide polymorphisms (SNP) are one variation of a single base pair in a DNA double strand. They are inherited and heritable genetic variants. Numerous studies have shown SNPs in various genes associated with the risk of developing autoimmune diseases. Here, the frequency of four such SNPs is reported in ME/CFS and healthy controls analysed comparatively. Since the onset of ME/CFS in approximately two thirds of patients is triggered by an infection, the stuy also investigated a possible connection with an infection-related disease outbreak.

Results:

A) ME/CFS patients have the risk variant of the SNP in PTPN22 significantly more often compared to healthy people (p = 0.033),

B) When dividing patients according to the type of disease outbreak, the investigators observed the accumulation of the risk variant only in patients with an infection-related onset of the disease (OR 1.63; p = 0.016), but not in patients without, in each case compared to healthy controls,

C) ME/CFS patients have the risk variant of the SNP in CTLA4 significantly more often compared to healthy people (p = 0.012),

D) The investigators observed the accumulation of the risk variant only in patients with an infection-related onset of the disease (OR = 1.53; p = 0.001), but not in those without, in each case compared to healthy controls,

E) Furthermore, the investigators found significant differences in the genotype distribution for the SNPs in CTLA4 and PTPN22 between ME/CFS patients with infection-related disease onset and healthy controls (CTLA4: p = 0.0061, PTPN22: p = 0.026), and

F) No association was found with the risk variants of SNPs in IRF5 and TNF in ME/CFS patients.

Conclusion:

A) The risk variants of the SNPs in PTPN22 and CTLA4 increase the risk of developing ME/CFS,

B) The risk variant in PTPN22 increases the likelihood of infection-related ME/CFS by 1.6-fold and that in CTLA4 by 1.5-fold, and

C) The results provide evidence for a genetic predisposition to infection-related ME/CFS and suggest a role for autoreactive Immune cells are involved in this disease mechanism.

(Description adapted from project website: see link above)