Li Qiaoli, Du Jing, Feng Ruizhi, Xu Yao, Wang Haojue, Sang Qing, Xing Qinghe, Zhao Xinzhi, Jin Li, He Lin, Wang Lei
State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology (Q.L., R.F., Y.X., H.W., Q.S., L.J., L.W.), School of Life Sciences, Fudan University, Shanghai, 200032, China; Institutes of Biomedical Sciences (Q.L., R.F., Y.X., H.W., Q.S., Q.X., X.Z., L.H., L.W.), Fudan University, Shanghai, 200032, China; Bio-X Center (L.H.), Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200032, China; and NPFPC Laboratory of Contraception and Devices, Shanghai Institute of Planned Parenthood Research (J.D.), Shanghai 200032, China.
J Clin Endocrinol Metab. 2014 Feb;99(2):E234-40. doi: 10.1210/jc.2013-3685. Epub 2013 Dec 3.
Telomeres are specialized chromatin structures located at the ends of eukaryotic chromosomes, and telomere length plays a clear role in various diseases. However, it is not known whether telomere length is related to polycystic ovary syndrome (PCOS).
We hypothesized that leukocyte telomere length (LTL) plays an important role in the pathophysiology of PCOS.
We used an established and validated quantitative PCR technique to measure the mean LTL in a large sample of PCOS patients and controls. We used logistic regression and multiple linear regression to analyze the association of PCOS and several related clinical parameters with the age-adjusted ratio of the telomere repeat length to the copy number of a single-copy gene (T/S).
Individuals with PCOS (n = 698) exhibited significantly shorter LTLs than the controls (n = 611) after adjusting for age (0.764 ± 0.016 vs 0.876 ± 0.023; P = .001; odds ratio = 1.403; 95% confidence interval, 1.150-1.712). The mean telomere length in the leukocytes of PCOS patients was comparable to that of control individuals who were on average 6.16 years older. Individuals having shorter telomere lengths (middle and lowest tertile) had significantly higher disease risk than those having the longest telomere length (highest tertile) (odds ratio = 1.614; 95% confidence interval, 1.262-2.066; P = .0001) after adjusting for age. In addition, a significant correlation between the LTL and the level of dehydroepiandrosterone sulfate was observed in controls (r = -0.185; P = .01).
We provide the first report that LTL is strongly associated with PCOS. This study suggests a new role for LTL in the pathophysiology of PCOS and might have important implications for our understanding of the etiology of the disease.
端粒是位于真核染色体末端的特殊染色质结构,端粒长度在多种疾病中发挥着明确作用。然而,尚不清楚端粒长度是否与多囊卵巢综合征(PCOS)相关。
我们假设白细胞端粒长度(LTL)在PCOS的病理生理学中起重要作用。
我们使用一种成熟且经过验证的定量PCR技术,测量大量PCOS患者和对照组的平均LTL。我们使用逻辑回归和多元线性回归分析PCOS及几个相关临床参数与端粒重复长度与单拷贝基因拷贝数的年龄校正比值(T/S)之间的关联。
校正年龄后,PCOS患者(n = 698)的LTL显著短于对照组(n = 611)(0.764±0.016对0.876±0.023;P = 0.001;比值比 = 1.403;95%置信区间,1.150 - 1.712)。PCOS患者白细胞中的平均端粒长度与平均年龄大6.16岁的对照个体相当。校正年龄后,端粒长度较短(中间和最低三分位数)的个体比端粒长度最长(最高三分位数)的个体具有显著更高的疾病风险(比值比 = 1.614;95%置信区间,1.262 - 2.066;P = 0.0001)。此外,在对照组中观察到LTL与硫酸脱氢表雄酮水平之间存在显著相关性(r = -0.185;P = 0.01)。
我们首次报告LTL与PCOS密切相关。本研究提示LTL在PCOS病理生理学中的新作用,可能对我们理解该疾病的病因具有重要意义。