Complement receptor 1 gene polymorphisms in sarcoidosis.
Sarcoidosis is likely to result from exposure of genetically susceptible hosts to environmental agents. Erythrocyte (E) complement receptor 1 (CR1) is a membrane protein mediating the transport of immune complexes (ICs) to phagocytes, and at least three polymorphisms on the CR1 gene are related to erythrocyte surface density of CR1 molecules, in turn related to the rate of IC clearance from circulation. We hypothesized that sarcoidosis could be associated with increased frequency of the CR1 gene alleles coding for reduced CR1/E ratio. We studied 91 sarcoid patients and two control groups: 94 healthy volunteers and 71 patients with chronic obstructive pulmonary disease (COPD). Three polymorphic sites of CR1 gene, His1208Arg, intron 27 HindIII/RFLP, and Pro1827Arg, were analyzed. The three polymorphisms were in linkage disequilibrium. The GG genotype for the Pro1827Arg (C(5507)G) polymorphism was significantly associated with sarcoidosis in comparison to both control groups (odds ratio [OR] = 3.13; 95% confidence interval [CI] 1.49-6.69 versus healthy control subjects, and OR= 2.82, 95% CI 1.27-6.39 versus COPD control subjects). The same genotype was particularly associated to disease in females (OR = 7.05; 95% CI 3.10-16.61 versus healthy control subjects). These findings agree with speculations on the role of CR1 gene as a possible susceptibility factor.
Zorzetto
Michele
M
Laboratorio di Biochimica e Genetica, Clinica di Malattie dell'Apparato Respiratorio, Pavia, Italy.
Bombieri
Cristina
C
Ferrarotti
Ilaria
I
Medaglia
Sara
S
Agostini
Carlo
C
Tinelli
Carmine
C
Malerba
Giovanni
G
Carrabino
Natalia
N
Beretta
Anna
A
Casali
Lucio
L
Pozzi
Ernesto
E
Pignatti
Pier Franco
PF
Semenzato
Gianpietro
G
Cuccia
Maria Clara
MC
Luisetti
Maurizio
M
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D000936:Antigen-Antibody Complex / Q000235:genetics / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D008657:Metabolic Clearance Rate; D011110:Polymorphism, Genetic; D011951:Receptors, Complement / Q000235:genetics* / Q000276:immunology; D012507:Sarcoidosis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D012737:Sex Factors
D000936:Antigen-Antibody Complex; D011951:Receptors, Complement