MCP-1 and MIP-1A gene polymorphisms in Japanese patients with sarcoidosis.
OBJECTIVE
Monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha exhibit chemotactic activity toward macrophages/monocytes and induce the production of inflammatory cytokines affecting granuloma formation. Recently, a single nucleotide polymorphism (SNP) in the MCP-1 distal regulatory region and a dinucleotide repeat in the MIP-1A gene promoter region were identified. We investigated the relationships between the polymorphisms and susceptibility to sarcoidosis, clinical manifestations, and BALF findings of sarcoidosis.


METHODS
The polymorphisms of the MCP-1 and MIP-1A genes in 118 patients with sarcoidosis and 145 healthy control subjects were examined. The MCP-1 polymorphism was genotyped by a PCR-restriction fragment length polymorphism method and the MIP-1A genotype was determined using PCR.


RESULTS
No significant difference in the genotype distribution or in the allele frequency between the patients and control subjects was observed. We found no relationship between the polymorphisms and the serum ACE level, organ involvement, roentgenographic stages, or deterioration in chest radiographs during the follow-up. A significant difference in the absolute counts of AMs in BALF of 51 patients among the genotypes of the MCP-1 gene was found (p = 0.048). The AM counts in BALF of the G/A and G/G genotypes were significantly increased compared with that of the A/A genotype (p < 0.05).


CONCLUSIONS
The polymorphisms of the MCP-1 and MIP-1A genes do not play a substantial role in genetic predisposition for sarcoidosis or in clinical manifestations of sarcoidosis in this Japanese population. The MCP-1 SNP might be related to the recruitment of monocytes/macrophages to the alveolar spaces in sarcoidosis.
Takada
Toshinori
T
Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University.
Suzuki
Eiichi
E
Morohashi
Kazuaki
K
Omori
Kentaro
K
Gejyo
Fumitake
F
D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018932:Chemokine CCL2 / Q000235:genetics*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004247:DNA / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017565:Sarcoidosis, Pulmonary / Q000208:ethnology / Q000235:genetics*
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D004247:DNA