Associations between sarcoidosis clinical course and ANXA11 rs1049550 C/T, BTNL2 rs2076530 G/A, and HLA class I and II alleles.
BACKGROUND
A genetic background may be responsible for the different clinical courses in sarcoidosis. We analyzed associations between sarcoidosis clinical course and HLA class I/II alleles and susceptibility gene SNPs ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A in a Portuguese population, investigating possible gene-gene interactions.


METHODS
We studied 138 unrelated Caucasian sarcoidosis patients (78 women, 56.5%; mean age, 37.2 ± 12.1 years). Disease that persisted after 2 years was considered chronic. Samples were genotyped for ANXA11 rs1049550 C/T and BTNL2 rs2076530 G/A SNPs using TaqMan Real-Time PCR Assays. HLA class I/II alleles were typed using PCR sequence-specific primers.


RESULTS
Sixty-six patients experienced disease resolution and 72 (52%) developed chronic disease. Comparison of rs1049550 and rs2076530 allele frequencies showed no significant differences. Only the HLA DRB1*03 allele was significantly associated with disease resolution (21.2% vs 4.9% for chronic disease; RR = 0.35; P < .01 after Bonferroni correction). In the logistic regression models evaluating the association between HLA alleles and chronic sarcoidosis adjusted for rs1049550 and rs2076530, only DRB1*03 was significantly associated with disease resolution. No significant interactions were found in any of the logistic regression analyses.


CONCLUSIONS
In this population of Caucasian patients with sarcoidosis, only DRB1*03 was associated with disease resolution after 2 years' follow-up, with no significant interactions found for susceptibility gene SNPs ANXA11 rs1049550 or BTNL2 rs2076530.
Pneumology Department, Centro Hospitalar Sao Joao, Porto, Portugal.|Faculty of Medicine, University of Porto, Portugal.
Antonio
A
Morais
Oficina de Bioestatistica, Ermesinde, Portugal.
Bruno
B
Lima
Unidade da Promoção da Saúde e Prevenção de Doenças Não Transmissiveis. Instituto Nacional de Saude (INSA) Dr. Ricardo Jorge, Porto, Portugal.
Helena
H
Alves
Pneumology Department, Centro Hospitalar Sao Joao, Porto, Portugal.
Natalia
N
Melo
Pneumology Department, Centro Hospitalar Sao Joao, Porto, Portugal.|Faculty of Medicine, University of Porto, Portugal.|Oficina de Bioestatistica, Ermesinde, Portugal.
Patricia C
PC
Mota
Pneumology Department, Centro Hospitalar Sao Joao, Porto, Portugal.|Faculty of Medicine, University of Porto, Portugal.
Agostinho
A
Marques
Immunology Lab, Basic & Clinical Immunology Unit, Faculty of Medicine, and Center for Health Technology and Services Research (CINTESIS), University of Porto, Portugal.
Luis
L
Delgado
D000328:Adult; D000483:Alleles; D000071797:Butyrophilins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011174:Portugal / Q000453:epidemiology; D012507:Sarcoidosis / Q000000981:diagnostic imaging / Q000208:ethnology* / Q000235:genetics*; D044465:White People / Q000235:genetics
C408263:BTNL2 protein, human; D000071797:Butyrophilins; D059811:HLA-DRB1 Chains