Epistatic interaction between FCRL3 and MHC in Spanish patients with IBD.
Inflammatory bowel disease (IBD), which comprises ulcerative colitis (UC) and Crohn's disease (CD), shows a multifactorial origin, with genetic and environmental factors involved. Although the genetic influence is clear for both diseases, the genetics involved is complex and epistatic interactions with other genes probably exist. The Fc receptor-like 3 gene (FCRL3) maps to the human chromosome 1q21-22 and certain single nucleotide polymorphisms (SNPs) in its promoter have been associated with some autoimmune diseases. Our aim was to study the role of two promoter SNPs of the FCRL3 gene (-169A>G, rs7528684 and -110C>T, rs11264799) in patients with IBD and their interaction with HLA-DRB1 and CARD15 in patients with UC and CD, respectively. A case-control study with 311 patients with CD, 324 patients with UC and 497 healthy controls was performed. All the individuals were White Spaniards. No significant associations were found between any FCRL3 SNP and CD or UC, but the stratification in patients with UC by human leukocyte antigen (HLA) showed a significant increase in heterozygosity at the FCRL3 locus, especially -169 AG (AG vs AA+GG, P= 0.0027, odds ratio = 3.6, 95% confidence interval 1.4-2.9), when HLA-DRB1*0103 carrier patients were compared with HLA-DRB1*0103 noncarriers. Our data suggest an epistatic interaction between genes in chromosomes 6p21 and 1q21-22, marked, respectively, by HLA-DRB1*0103 and FCRL3-169 AG.
Martínez
A
A
Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain. alfmdoncel@terra.es
Núñez
C
C
Martín
M C
MC
Mendoza
J L
JL
Taxonera
C
C
Díaz-Rubio
M
M
de la Concha
E G
EG
Urcelay
E
E
D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006579:Heterozygote; D006649:Histocompatibility Antigens / Q000235:genetics*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000208:ethnology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic / Q000235:genetics*; D013030:Spain
C457775:FCRL3 protein, human; D006680:HLA Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006649:Histocompatibility Antigens; D011971:Receptors, Immunologic