Interrogating Genetic Susceptibility Loci in CVID and Autoimmunity
Sunday, March 6, 2016: 2:30 PM
Room 408A (Convention Center)
Luanna Yang, , , , , , , ,
Rationale: G protein signaling modulator-3 (GPSM3) is a GoLoco protein that regulates GPCR signaling and is highly expressed in immune cells. Two single nucleotide polymorphisms within the GPSM3 gene (SNPs rs204989, rs204991) are in perfect linkage disequilibrium, inherited together as a single protective allele, and have been associated with a decreased prevalence of some autoimmune diseases in the general population.  Consequently, we hypothesized that possessing the allele may correlate with decreased autoimmunity in CVID.

Methods: Forty-six Caucasian CVID patients were recruited from UNC and Duke. Blood leukocytes were genotyped, assaying genomic DNA for rs204989 SNP using manufacturer protocols. A retrospective chart review was conducted to determine whether patients had autoimmune disease.

Results:  Of the 46 CVID patients, 29 (63%) did not have the protective GPSM3 allele (SNPM/M), 13 (28%) possessed one allele (SNPM/m), and 4 (9%) possessed both alleles (SNPm/m).  17 of the 46 CVID patients had autoimmunity (37%), and 2 had lymphoproliferation (4%). Four of 17 autoimmune patients (23%) possessed at least one copy of the protective allele (SNPm/m or SNPM/m) compared to 11 of 27 non-autoimmune patients (41%). Both lymphoproliferative patients were heterozygous (SNPM/m).

 Conclusions:  CVID patients with autoimmunity are less likely to possess the GPSM3 protective allele (SNPm/m or SNPM/m).  Interestingly, SNP prevalence in CVID was increased overall compared to healthy Caucasians (9% versus 2% SNPm/m and 28% versus 24% SNPM/m), and both lymphoproliferative patients were SNPM/m heterozygous.  This observation suggests that this specific GPSM3 allele may be enriched in CVID compared to the general population and could have functional significance.