BTNL2 gene G16071A SNP seems to be a predisposing factor for sarcoidosis except in Caucasian postmenopausal women with sarcoid uveitis in whom the GG genotype prevails.
We analyzed associations between sarcoidosis clinical course and HLA class I/II alleles and susceptibility gene SNPs ANXA11 rs1049550 C/T and BTNL2rs2076530 G/A in a Portuguese population, investigating possible gene-gene interactions.
The meta-analysis indicated that BTNL2G16071A gene polymorphism may as a likelihood factor contributed to granulomatous disease susceptibility, especially increasing the sarcoidosis susceptibility.
These results confirm the association of BTNL2 rs2076530SNP with the susceptibility to develop sarcoidosis, but not with an increased risk of cancer in these patients.
Both BTNL2 SNPs were associated with risk of sarcoidosis in separate models, but in a combined analysis the increased risk was due to the A-allele of the rs3817963 SNP; each copy of the A-allele was associated with a 40 % increase in risk of sarcoidosis (p = 0.02) and was confirmed by our haplotypic analysis.
The purpose of our study was to verify the relationship between BTNL2 and HLA risk alleles for the susceptibility to sarcoidosis, and to assess whether the BTNL2 association is independent of the HLA risk alleles.
The CNV_ID 507, which was highlighted for its possible involvement in sarcoidosis because of its partly deletion of the BTNL2 gene, was tested for association in a cohort of 89 sarcoidosis patients and 89 matched controls, but our results indicated that CNV_ID 507 does not affect the genomic structure of BTLN2 as previously described.
The CNV_ID 507, which was highlighted for its possible involvement in sarcoidosis because of its partly deletion of the BTNL2 gene, was tested for association in a cohort of 89 sarcoidosis patients and 89 matched controls, but our results indicated that CNV_ID 507 does not affect the genomic structure of BTLN2 as previously described.
Our data suggest that the absence of a membrane anchored BTNL2 protein may increase genetic susceptibility to sarcoidosis and familial occurrence of the disease.
Butyrophilin-like 2 (BTNL2) is a butyrophilin family member with homology to the B7 costimulatory molecules, polymorphisms of which have been recently associated through genetic analyses to sporadic inclusion body myositis and sarcoidosis.
Genome-wide screening has conclusively identified linkage to chromosome 5q11and the development of sarcoidosis, and HLA genes and BTNL2 are susceptibility genes located in this region.
A recent study of sarcoidosis has provided evidence of an independent effect, associated with a truncating single nucleotide polymorphism (SNP) of a nearby gene, BTNL2.
BTNL2 haplotype 4, tagged by the rs2076530 G allele, also remained associated with non-Löfgren sarcoidosis after adjusting for HLA-DRB1 alleles (OR 0.37, P = 0.016).