Ziółkowska-Suchanek Iwona, Mosor Maria, Gabryel Piotr, Grabicki Marcin, Żurawek Magdalena, Fichna Marta, Strauss Ewa, Batura-Gabryel Halina, Dyszkiewicz Wojciech, Nowak Jerzy
Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, Poznań, Poland.
Department of Thoracic Surgery, University of Medical Sciences, 62 Szamarzewskiego Street, 60-569 Poznań, Poland.
Sci Rep. 2015 Aug 27;5:13502. doi: 10.1038/srep13502.
Genome-wide association studies have identified loci at 15q25 (IREB2) and 4q22 (FAM13A), associated with lung cancer (LC) and chronic obstructive pulmonary disease (COPD). The aim of our research was to determine the association of IREB2 and FAM13A SNPs with LC and severe/very severe COPD patients. We examined IREB2 variants (rs2568494, rs2656069, rs10851906, rs13180) and FAM13A (rs1903003, rs7671167, rs2869967) among 1.141 participants (468 LC, 149 COPD, 524 smoking controls). The frequency of the minor IREB2 rs2568494 AA genotype, was higher in LC vs controls (P = 0.0081, OR = 1.682). The FAM13A rs2869967 was associated with COPD (minor CC genotype: P = 0.0007, OR = 2.414). The rs1903003, rs7671167 FAM13A variants confer a protective effect on COPD (both P < 0.002, OR < 0.405). Haplotype-based tests identified an association of the IREB2 AAAT haplotype with LC (P = 0.0021, OR = 1.513) and FAM13A TTC with COPD (P = 0.0013, OR = 1.822). Cumulative genetic risk score analyses (CGRS), derived by adding risk alleles, revealed that the risk for COPD increased with the growing number of the FAM13A risk alleles. OR (95% CI) for carriers of ≥5 risk alleles reached 2.998 (1.8 to 4.97) compared to the controls. This study confirms that the IREB2 variants contribute to an increased risk of LC, whereas FAM13A predisposes to increased susceptibility to COPD.
全基因组关联研究已经确定了位于15q25（IREB2）和4q22（FAM13A）的基因座，它们与肺癌（LC）和慢性阻塞性肺疾病（COPD）相关。我们研究的目的是确定IREB2和FAM13A单核苷酸多态性（SNP）与LC患者以及重度/极重度COPD患者之间的关联。我们检测了1141名参与者（468名LC患者、149名COPD患者、524名吸烟对照者）的IREB2变异体（rs2568494、rs2656069、rs10851906、rs13180）和FAM13A（rs1903003、rs7671167、rs2869967）。与对照相比，LC患者中IREB2次要等位基因rs2568494的AA基因型频率更高（P = 0.0081，比值比[OR]=1.682）。FAM13A的rs2869967与COPD相关（次要CC基因型：P = 0.0007，OR = 2.414）。FAM13A的rs1903003、rs7671167变异体对COPD有保护作用（P均<0.002，OR<0.405）。基于单倍型的检测确定IREB2的AAAT单倍型与LC相关（P = 0.0021，OR = 1.513），FAM13A的TTC单倍型与COPD相关（P = 0.0013，OR = 1.822）。通过累加风险等位基因得出的累积遗传风险评分分析（CGRS）显示，COPD的风险随着FAM13A风险等位基因数量的增加而升高。与对照相比，携带≥5个风险等位基因者的OR（95%置信区间）达到2.998（1.8至4.97）。本研究证实，IREB2变异体增加LC风险，而FAM13A使个体更易患COPD。
