title: SLC11A1 polymorphisms are associated with the risk of chronic obstructive pulmonary disease in a Korean population.
abstract: The solute carrier family 11 member 1 (SLC11A1) protein plays important roles in macrophage activation and displays pleiotropic effects on various macrophage functions, including the regulation of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and oxidative burst. Considering the important roles of macrophage in the pathogenesis of chronic obstructive pulmonary disease (COPD), we hypothesized that the SLC11A1 gene may act as a low-penetrance susceptibility gene for COPD. To test this hypothesis, we first examined the frequencies of 12 candidate polymorphisms in the SLC11A1 gene in 27 healthy Korean individuals, and then genotyped 3 haplotype-tagging polymorphisms [IVS4 + 14G > C (rs3731865), D543 N (rs17235409), and (*)86A > G (rs1059823)] in 83 COPD patients and 203 healthy controls. Individuals with at least one variant allele of the D543 N and (*)86A > G polymorphisms were at a significantly increased risk for COPD compared with carriers with each homozygous wild-type allele [adjusted odds ratio (OR) = 2.23, 95% confidence interval (CI) = 1.24-4.02, P = 0.007; and adjusted OR = 1.92, 95% CI = 1.10-3.35, P = 0.022, respectively]. Consistent with the findings of the genotyping analysis, the 122 haplotype carrying both the 543 N and (*)86G alleles was associated with a significantly increased risk for COPD compared with the 111 haplotype with the 542D and (*)86A alleles (adjusted OR = 2.05, 95% CI = 1.19-3.51, P = 0.009 and Bonferroni corrected P = 0.027). These findings suggest that the SLC11A1 polymorphisms could be used as markers for genetic susceptibility to COPD. However, further studies with large numbers of subjects are needed to confirm our findings.
authors.affiliation: Department of Internal Medicine, Kyungpook National University Hospital, Samduk 2 Ga 50, Daegu, 700-412, South Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Kim
authors.forename: Kyung Mee
authors.initials: KM
authors.lastname: Kim
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Park
authors.forename: Jong Sik
authors.initials: JS
authors.lastname: Kim
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.forename: Sung Ick
authors.initials: SI
authors.lastname: Cha
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.forename: Sung Beom
authors.initials: SB
authors.lastname: Han
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Jung
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000235:genetics*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1