[6ZCo3xuK]

Macrophage receptor gene variant influences COPD susceptibilityBy Joel Levy11 May 2010Chest 2010; 137: 1098?1107MedWire News:

A single nucleotide polymorphism (SNP) in the macrophage scavenger receptor-1 gene (MSR1) is associated with susceptibility to chronic obstructive pulmonary disease (COPD), a US study has found.

The MSR1 SNP is also associated with abnormalities of macrophage function in vitro.

Smokers often develop COPD in a familial pattern, suggesting a strong genetic component in susceptibility to the disease. Previous studies have revealed that MSR1 is in a genomic region linked to COPD susceptibility and may be a candidate gene for COPD.

To evaluate the role of polymorphisms in MSR1 in COPD, a team led by Jill Ohar, from Wake Forest University School of Medicine in Winston-Salem, North Carolina, genotyped 714 smokers (of at least 20 pack-years) over the age of 40 years, and examined in vitro survival, adhesion, and receptor expression of macrophages from donors with specific at-risk genotypes.

The MSR1 coding SNP, P275A, was significantly associated with susceptibility to COPD in smokers, with the rare CG genotype found in 13.1% of patients compared with just 5.2% of controls. The CG genotype of SNP P275A, compared with the CC genotype, was also associated with lower percentage of predicted FEV1 (68.0 vs 71.7), FEV1/forced vital capacity (66.2 vs 67.4), and forced expiratory flow (FEF)25-75 (45.7 vs 53.4).

Monocytes were isolated from seven P275A CG/GG and eight P275A CC controls and cultured to generate monocyte-derived macrophages. Compared with controls, the P275A CG/GG genotype was associated with increases in maintenance of cell number in culture (increased survival/reduced apoptosis), MSR1 expression, and adhesion of macrophages to plastic in vitro.

Macrophage accumulation in the lungs has been linked to COPD. Writing in the journal Chest, the researchers comment that their findings in relation to the P275A CG/GG MSR1 genotype ?provide a mechanism for not only increased recruitment, but also decreased clearance of macrophages in the lung in COPD.?

They conclude: ?The MSR1 association with COPD susceptibility, COPD-related measures of lung function, and abnormalities of macrophage function may account for significant COPD morbidity.?