SLC11A1 polymorphisms are associated with the risk of chronic obstructive pulmonary disease in a Korean population.
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.
Kim
Eun Jin
EJ
Department of Internal Medicine, Kyungpook National University Hospital, Samduk 2 Ga 50, Daegu, 700-412, South Korea.
Kim
Kyung Mee
KM
Park
Sun Ha
SH
Kim
Jong Sik
JS
Lee
Won Kee
WK
Cha
Sung Ick
SI
Kim
Chang Ho
CH
Kang
Young Mo
YM
Han
Sung Beom
SB
Jung
Tae Hoon
TH
Park
Jae Yong
JY
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
D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1