Contribution of an adenine to guanine single nucleotide polymorphism of the matrix metalloproteinase-13 (MMP-13) -77 promoter region to the production of anticyclic citrullinated peptide antibodies in patients with HLA-DRB1*shared epitope-negative rheumatoid arthritis.
We examined whether matrix metalloproteinase-13 (MMP-13) contributes to disease susceptibility or severity of rheumatoid arthritis (RA). Eighty-seven patients with RA whose disease duration was <2 years and 71 healthy controls were enrolled in the study. Adenine (A) to guanine (G) single nucleotide polymorphism (SNP) of the -77 MMP-13 promoter region in RA and healthy controls was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Human leukocyte antigen (HLA)-DRB1 genotyping was also performed using the same populations. Anticyclic citrullinated peptide (anti-CCP) antibodies from RA patients at entry were studied, and their relationships were examined. The genotype and allele frequency of SNP of MMP-13 at -77 did not differ between RA patients and healthy controls. We focused on the RA patients who were negative for HLA-DRB1*shared epitope (SE) alleles and found that the seropositivity of anti-CCP antibodies with a titer >25 U/ml was high in the A/A genotype compared with the G/G genotype. The same characteristic was also found in HLA-DRB1*0405 allele-negative patients. Our data suggest that SNP of the -77 MMP-13 promoter region acts as a surrogate marker of anti-CCP antibody production in HLA-DRB1*SE allele-negative RA patients, which may reflect RA severity.
Unit of Translational Medicine, Department of Immunology and Rheumatology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. naoki_iwa@hotmail.com
Naoki
N
Iwamoto
Atsushi
A
Kawakami
Kazuhiko
K
Arima
Mami
M
Tamai
Hideki
H
Nakamura
Shin-ya
SY
Kawashiri
Junko
J
Kita
Akitomo
A
Okada
Tomohiro
T
Koga
Makoto
M
Kamachi
Satoshi
S
Yamasaki
Kunihiro
K
Ichinose
Hiroaki
H
Ida
Tomoki
T
Origuchi
Katsumi
K
Eguchi
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics* / Q000276:immunology*; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D012720:Severity of Illness Index
D001323:Autoantibodies; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13