Evaluating the role of the genetic variations of PTPN22, NFKB1, and FcGRIIIA genes in inflammatory bowel disease: a meta-analysis.
BACKGROUND
We tested several polymorphisms of genes involved in the mucosal immune system in a population of inflammatory bowel disease (IBD) patients to investigate their possible implication in disease predisposition.


METHODS
Polymorphisms of 3 candidate genes (PTPN22, NFkB1, and FcGRIIIA) were investigated in 649 IBD patients (343 with Crohn's disease [CD] and 306 with ulcerative colitis [UC]), 176 unaffected relatives, and 256 healthy controls. Allele and genotype frequencies were correlated with clinical characteristics and major variants of the CARD15 gene. Our findings were pooled in a meta-analysis with the available studies in the literature.


RESULTS
No significant difference for the PTPN22 and NFkB1 variants was found. In contrast, allele and genotype frequencies of the G559T allele of the FcGRIIIA gene were significantly different in CD patients compared to controls (allele T 12% versus 8%, odds ratio [OR] = 1.58, 95% confidence interval [CI] 1.06-2.35; GT genotype 23% versus 16%, OR = 1.64, 95% CI = 1.08-2.5). However, no significant overtransmission of the T allele was confirmed at the family-based analysis. For all genes, neither an interaction with CARD15 gene, nor a significant difference at genotype/phenotype analysis was demonstrated, included response to medical therapy.


CONCLUSIONS
Although involved in autoimmune diseases, the PTPN22 and NFkB1 genes do not seem involved in the IBD predisposition, also according to meta-analysis results. The association with the G559T polymorphism of the FcGRIIIA gene in CD patients deserves further investigation.
Latiano
Anna
A
Unità Operativa di Gastroenterologia e Laboratorio di Ricerca Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Palmieri
Orazio
O
Valvano
Maria Rosa
MR
Bossa
Fabrizio
F
Latiano
Tiziana
T
Corritore
Giuseppe
G
DeSanto
Ermelinda
E
Andriulli
Angelo
A
Annese
Vito
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*
C496124:FCGR3A protein, human; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D017452:Receptors, IgG; D004247:DNA; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22