J Korean Med Sci.  2009 Dec;24(6):1119-1125. 10.3346/jkms.2009.24.6.1119.

SERPINE2 Polymorphisms and Chronic Obstructive Pulmonary Disease

• Cha SI
• Kang HG
• Choi JE
• Kim MJ
• Park J
• Lee WK
• Kim CH
• Jung TH
• Park JY

• KMID: 1783142
• DOI: http://doi.org/10.3346/jkms.2009.24.6.1119

Abstract

A number of genome-wide linkage analyses have identified the 2q33.3-2q37.2 region as most likely to contain the genes that contribute to the susceptibility to chronic obstructive pulmonary disease (COPD). It was hypothesized that the SERPINE2 gene, which is one of the genes located at the 2q33.3-2q37.2 region, may act as a low-penetrance susceptibility gene for COPD. To test this hypothesis, the association of four SERPINE2 single nucleotide polymorphisms (SNPs; rs16865421A>G, rs7583463A>C, rs729631C>G, and rs6734100C>G) with the risk of COPD was investigated in a case-control study of 311 COPD patients and 386 controls. The SNP rs16865421 was associated with a significantly decreased risk of COPD in a dominant model for the polymorphic allele (adjusted odds ratio [OR]=0.66, 95% confidence interval [CI]=0.45-0.97, P=0.03). In haplotype analysis, the GACC haplotype carrying the polymorphic allele at the rs16865421 was associated with a significantly decreased risk of COPD when compared to the AACC haplotype (adjusted OR=0.58, 95% CI=0.38-0.89, P=0.01), and this effect was evident in younger individuals (adjusted OR=0.30, 95% CI=0.14-0.64, P=0.002). This study suggests that the SERPINE2 gene contributes to the susceptibility to COPD.

Keyword

Serpine2; Polymorphism; Pulmonary Disease, Chronic Obstructive

MeSH Terms

Amyloid beta-Protein Precursor/*genetics
*Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Haplotypes
Humans
Linkage (Genetics)
Male
Middle Aged
*Polymorphism, Single Nucleotide
Pulmonary Disease, Chronic Obstructive/*genetics/pathology
Questionnaires
Receptors, Cell Surface/*genetics

Figure

• 

  Fig. 1 Linkage disequilibrium (LD) blocks between SERPINE2 polymorphisms in 27 healthy Koreans (A) and the subjects (n=697) of a case-control study (B). The LD blocks were generated by the Haploview program. Black boxes indicate complete LD (|D'|=1.0 and r2=1.0). Dark gray boxes indicate strong evidence of LD (confidence interval [CI] minima for strong LD: upper 0.98, low 0.7; fraction of strong LD in informative comparisons must be at least 0.95). White boxes indicate strong recombination (upper CI ≤0.9), and the gray boxes indicate uninformative findings. Triangles indicate haplotype blocks. Numbers in squares are |D'| (×100) values.

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