Correlation between Circadian Gene Variants and Serum Levels of Sex Steroids and Insulin-like Growth Factor-I
Correlation between Circadian Gene Variants and Serum Levels of Sex Steroids and Insulin-like Growth Factor-I
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DOI：
10.1158/1055-9965.epi-08-0073
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发表时间：
2008-11-01
影响因子：
3.8
通讯作者：
Hsing, Ann W.
中科院分区：
文献类型：
--
作者：
Chu, Lisa W.;Zhu, Yong;Hsing, Ann W.
包括类固醇激素分泌在内的各种生物过程都具有昼夜节律，这受到9种已知昼夜节律基因的影响。以前，我们报道过昼夜节律基因的某些变异与前列腺癌的风险有关。为了对这些发现提供一些生物学上的见解，我们检测了241名中国健康老年男性（平均年龄71.5岁）的5种昼夜节律基因变体，包括NPAS 2（rs 2305160：G>A）、PER 1（rs 2585405：G>C）、CSNK 1 E（rs 1005473：A>C）、PER 3（54-bp重复长度变体）和CRYS 2（rs 1401417：G>C），与血清性类固醇和胰岛素样生长因子（IGF）-I和IGF结合蛋白3（IGFBP 3）水平的关系。经方差分析和腰臀比调整后的似然比检验（LRT）显示，与GG基因型相比，NPAS 2变体A等位基因与较低的游离睾酮和生物可利用睾酮相关（P-LRT分别为0.02和0.01）。此外，PER 1变异体与血清性激素结合球蛋白水平升高（P趋势= 0.03）、5 α-雄甾烷-3 α，17 β-二醇葡糖苷酸水平降低（P趋势= 0.02）和IGFBP 3水平降低（P趋势= 0.05）相关。此外，与AA基因型相比，CSNK 1 E变体C等位基因与更高的睾酮/双氢睾酮比率（P-LRT = 0-01）相关，而更长的PER 3重复序列与更高的血清IGF-I水平（P-LRT = 0.03）和IGF-I/IGFBP 3比率（P-LRT = 0.04）相关。该基因的多态性与所分析的任何生物标志物无关。我们的研究结果，虽然需要确认，表明昼夜节律基因的变化与血清激素水平相关，为昼夜节律基因在乳腺癌相关癌症中的作用提供了生物学支持。（癌症流行病学生物标志物Prev 2008;17（11）：3268-73）
A variety of biological processes, including steroid hormone secretion, have circadian rhythms, which are influenced by nine known circadian genes. Previously, we reported that certain variants in circadian genes were associated with risk for prostate cancer. To provide some biological insight into these findings, we examined the relationship of five variants of circadian genes, including NPAS2 (rs2305160:G>A), PER1 (rs2585405:G>C), CSNK1E (rs1005473:A>C), PER3 (54-bp repeat length variant), and CRY2 (rs1401417:G>C), with serum levels of sex steroids and insulin-like growth factor (IGF)-I and IGF-binding protein 3 (IGFBP3) in 241 healthy elderly Chinese men (mean age of 71.5). Age-adjusted and waist-to-hip ratio-adjusted ANOVA followed by likelihood ratio tests (LRT) showed that the NPAS2 variant A allele was associated with lower free and bioavailable testosterone (P-LRT = 0.02 and 0.01, respectively) compared with the GG genotype. In addition, the PER1 variant was associated with higher serum levels of sex hormonebinding globulin levels (P-trend = 0.03), decreasing 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide levels (P-trend = 0.02), and decreasing IGFBP3 levels (P-trend = 0.05). Furthermore, the CSNK1E variant C allele was associated with higher testosterone to dihydrotestosterone ratios (P-LRT = 0-01) compared with the AA genotype, whereas the longer PER3 repeat was associated with higher serum levels of IGF-I (P-LRT = 0.03) and IGF-I to IGFBP3 ratios (P-LRT = 0.04). The CRY2 polymorphism was not associated with any biomarkers analyzed. Our findings, although in need of confirmation, suggest that variations in circadian genes are associated with serum hormone levels, providing biological support for the role of circadian genes in hormone-related cancers. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3268-73)