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.

Identification of key genes and biological pathways in chronic obstructive pulmonary disease using bioinformatics and next generation sequencing data analysis

“…Signaling pathways include immune system [109], signal transduction [110], extracellular matrix organization [111], adaptive immune system [112], neutrophil degranulation [113], innate immune system [114], metabolism [115], diseases of metabolism [116] and Hemostasis [117] were responsible for advancement of COPD. PTGS2 [118], IL6 [119], CSF3 [120], CXCL8 [121], CXCL1 [122], SOCS3 [123], CCL3 [124], CCL5 [125], VCAM1 [126], CXCL13 [127], CXCL5 [128], CXCL12 [129], FGG (fibrinogen gamma chain) [130], IL1B [131], AREG (amphiregulin) [132], SERPINE1 [133], OSM (oncostatin M) [134], CCL11 [135], MFAP4 [136], APLN (apelin) [137], IL1RN [138], IFNG (interferon gamma) [139], CX3CL1 [140], CDKN1A [141], ICAM1 [142], SNAI1 [143], CD34 [144], IL33 [145], FASLG (Fas ligand) [146], FGF7 [147], TNF (tumor necrosis factor) [148], GDF15 [149], CCL22 [150], IL2 [151], CXCR6 [152], KLF5 [153], MCL1 [154], SRF (serum response factor) [155], FABP4 [156], CYP2C19 [157], CXCR4 [158], FOXC1 [159], EPHX1 [160], ANXA1 [161], DUSP6 [162], CPA3 [163], MYH10 [164], ICOS (inducible T cell costimulator) [165], CD1C [166], CD96 [167], S100A9 [168], FKBP5 [169], HMOX1 [170], PRTN3 [171], MARCO (macrophage receptor with collagenous structure) [172], STAB1 [173], SIGLEC9 [174], SLC11A1 [175], BPI (bactericidal permeability increasing protein) [176], PGF (placental growth factor) [177], FASN (fatty acid synthase) [178], S100A4 […”

Correlation of Polymorphisms of Natural Resistance-Associated Macrophage Protein 1 (NRAMP1) Gene and Smoking with the Risk of Rheumatoid Arthritis in Chinese Han People

“…A study investigating the possible function of NRAMP1 gene polymorphisms in susceptibility and clinical outcome of RA for a Spanish population was performed by Rodriguez et al [21], and found effects on RA with radiological severity by promoter polymorphisms NRAMP1 gene. Rs1059823 has been reported to be associated with tuberculosis in East India [22], type 1 diabetes of European ancestry population [23], and chronic obstructive pulmonary disease of a Korean population [24].…”