Tacheva Tanya, Zienolddiny Shanbeh, Dimov Dimo, Vlaykova Denitsa, Vlaykova Tatyana
Department of Medical Chemistry and Biochemistry, Medical Faculty, Trakia University, Stara Zagora, Bulgaria.
Section for Toxicology and Biological Work Environment, National Institute of Occupational Health, Oslo, Norway.
PeerJ. 2021 Nov 11;9:e12190. doi: 10.7717/peerj.12190. eCollection 2021.
Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and is associated with chronic local and systemic inflammation and oxidative stress. The enhanced oxidative stress and inflammation have been reported to affect telomere length (TL). Furthermore, a number of SNPs at loci encoding the main components of the telomerase genes, and have been shown to correlate with TL. We aimed to explore the leukocyte TL and genotypes for single nucleotide polymorphisms, rs12696304 (C > G) and rs10936599 (C > T) near in COPD cases and matched healthy controls using q-PCR technologies. Successful assessment of TL was performed for 91 patients and 88 controls. The patients had shorter TL (17919.36 ± 1203.01 bp) compared to controls (21 271.48 ± 1891.36 bp) although not significant ( = 0.137). The TL did not associate with the gender, age, spirometric indexes, smoking habits but tended to correlate negatively with BMI (Rho = - 0.215, = 0.076) in the controls, but not in COPD patients. The genotype frequencies of the SNPs rs12696304 and rs10936599 were compared between patients and controls and the odds ratios (OR) for developing COPD were calculated. The carriers of the common homozygous (CC) genotypes of the SNPs had higher risk for COPD, compared to carriers of the variants alleles (rs12696304 CG+GG CC; OR: 0.615, 95% CI [0.424-0.894], = 0.011 and for rs10936599 CT+TT CC OR = 0.668, 95% CI [0.457-0.976], = 0.044). Analysis on the combined effects of the rs12696304 (C > G) and rs10936599 (C > T) genotypes, CC/CC genotype combination was associated with higher risk for COPD ( < 0.0001) and marginally lower FEV1% pr. in patients with GOLD II ( = 0.052). There was no association between the SNP genotypes and TL. In summary, our results suggest that COPD patients may have shorter TL, and rs12696304 and rs10936599 near may affect the risk of COPD independently of TL.
慢性阻塞性肺疾病(COPD)的特征是气流不可逆性阻塞,并与慢性局部和全身炎症以及氧化应激相关。据报道,氧化应激和炎症增强会影响端粒长度(TL)。此外,已证明端粒酶基因主要成分编码位点的多个单核苷酸多态性(SNP)与TL相关。我们旨在使用定量聚合酶链反应(q-PCR)技术,探索COPD患者及匹配的健康对照者中白细胞TL以及单核苷酸多态性rs12696304(C>G)和rs10936599(C>T)的基因型。对91例患者和88例对照者成功进行了TL评估。与对照组(21271.48±1891.36 bp)相比,患者的TL较短(17919.36±1203.01 bp)(P=0.137),差异无统计学意义。在对照组中,TL与性别、年龄、肺功能指标、吸烟习惯无关,但与体重指数呈负相关(Rho=-0.215, P=0.076),而在COPD患者中无此相关性。比较了患者和对照者中SNP rs12696304和rs10936599的基因型频率,并计算了患COPD的比值比(OR)。与变异等位基因携带者相比,SNP常见纯合(CC)基因型携带者患COPD的风险更高(rs12696304:CG+GG对CC;OR:0.615,95%置信区间[0.424-0.894],P=0.011;rs10936599:CT+TT对CC,OR=0.668,95%置信区间[0.457-0.976],P=0.044)。分析rs12696304(C>G)和rs10936599(C>T)基因型的联合效应,CC/CC基因型组合与患COPD的风险较高相关(P<0.0001),且在GOLD II级患者中第一秒用力呼气容积百分比(FEV1%)略低(P=0.052)。SNP基因型与TL之间无关联。总之,我们的结果表明,COPD患者的TL可能较短,且rs12696304和rs10936599附近区域可能独立于TL影响COPD的发病风险。