PTEN identified as important risk factor of chronic obstructive pulmonary disease.

PTEN identified as important risk factor of chronic obstructive pulmonary disease.
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DOI:
10.1016/j.rmed.2009.06.016
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发表时间:
2009-12
影响因子:
4.3
通讯作者:
Lan, Qing
Lan, Qing
中科院分区:
医学3区
文献类型:
--
作者:
Hosgood, H. Dean, III;Menashe, Idan;He, Xingzhou;Chanock, Stephen;Lan, Qing

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常见的遗传变异可能在改变慢性阻塞性肺病(COPD)风险方面发挥重要作用。在中国宣威,慢性阻塞性肺病发病率是中国全国平均水平的两倍多,并且慢性阻塞性肺病与家庭煤炭使用密切相关。为了确定家庭中大量接触煤烟的人群中可能与 COPD 相关的遗传变异,我们在宣威进行了一项基于人群的病例对照研究(53 例病例;107 例对照),评估了 380 个可能与癌症和其他人类疾病相关的候选基因中的 1,261 个单核苷酸多态性 (SNP)。在使用 20,000 次排列的 minP 分析中,PTEN 是与 COPD 最显着相关的基因 (P = 0.00005)。基于 SNP 的分析发现,PTEN rs701848 纯合子变异携带者(ORTT = 0.12,95% CI = 0.03 - 0.47)患 COPD 的风险显着降低。 PTEN(或磷酸酶和张力蛋白同源物)是通过 AKT 信号通路调节细胞周期进程和细胞存活的重要调节因子。我们的探索性分析表明PTEN基因变异可能是宣威地区COPD的重要危险因素。然而,由于样本量较小,需要进行更多研究来评估宣威和其他煤烟暴露人群中的这些关联。
Common genetic variation may play an important role in altering chronic obstructive pulmonary disease (COPD) risk. In Xuanwei, China, the COPD rate is more than twice the Chinese national average, and COPD is strongly associated with in-home coal use. To identify genetic variation that may be associated with COPD in a population with substantial in-home coal smoke exposures, we evaluated 1,261 single nucleotide polymorphisms (SNPs) in 380 candidate genes potentially relevant for cancer and other human diseases in a population-based case-control study in Xuanwei (53 cases; 107 controls). PTEN was the most significantly associated gene with COPD in a minP analysis using 20,000 permutations (P = 0.00005). SNP-based analyses found that homozygote variant carriers of PTEN rs701848 (ORTT = 0.12, 95%CI = 0.03 - 0.47) had a significant decreased risk of COPD. PTEN, or phosphatase and tensin homolog, is an important regulator of cell cycle progression and cellular survival via the AKT signaling pathway. Our exploratory analysis suggests that genetic variation in PTEN may be an important risk factor of COPD in Xuanwei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuanwei and other populations with coal smoke exposures.
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