title: Genetic variations in scavenger and β₂-adrenergic receptors and risk of pulmonary disease.
abstract: Chronic obstructive pulmonary disease (COPD) is a complex disease with many pathological components. Familial clustering indicates that genetic susceptibility may be important for the development of the disease. Genes encoding scavenger and β2-adrenergic receptors are plausible candidate genes in COPD. Using data from two large Danish general population studies, we studied rare functional variants in the genes encoding scavenger receptor A-I/II (SRA-I/II), macrophage receptor with collagenous structure (MARCO), and the β2-adrenergic receptor (ADRB2) for associations with lung function and risk of COPD. We found that the truncating variant Arg293X in the gene encoding SRA-I/II was associated with reduced lung function and with increased risk of COPD among men, as well as among α1-antitrypsin MZ and superoxide dismutase-3 E1I1 heterozygotes. However, none of the nonsynonymous variants discovered by resequencing of the structurally similar MARCO were associated with lung function or risk of COPD. Finally, we found that the rare Thr164Ile polymorphism in ADRB2 was associated with reduced lung function and risk of COPD, whereas the more common Gly16Arg and Gln27Glu were not. Further studies are needed to confirm these relationships.
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark. mettethomsen78@gmail.com.
authors.forename: Mette
authors.initials: M
authors.lastname: Thomsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000235:genetics / Q000503:physiopathology; D003718:Denmark; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D012307:Risk Factors; D051117:Scavenger Receptors, Class A / Q000235:genetics*; D013147:Spirometry
chemical_list: C553443:ADRB2 protein, human; D005819:Genetic Markers; C490460:MARCO protein, human; C495139:MSR1 protein, human; D018343:Receptors, Adrenergic, beta-2; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A