Correlation between Circadian Gene Variants and Serum Levels of Sex Steroids and Insulin-like Growth Factor-I

Chu, Lisa W.; Zhu, Yong; Yu, Kai; Zheng, Tongzhang; Chokkalingam, Anand P.; Stanczyk, Frank Z.; Gao, Yu‐Tang; Hsing, Ann W.

doi:10.1158/1055-9965.epi-08-0073

Cited by 31 publications

(24 citation statements)

References 37 publications

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“…68 In terms of effects on physiology, NPAS2 394 Thr correlates with lower and bioavailable testosterone, providing support for a role for NPAS2 in hormone-related cancers. 69 Another intronic SNP in NPAS2 has been shown to be significantly associated with susceptibility to prostate cancer as well. 23 …”

Section: Npas2mentioning

confidence: 99%

“…64 PER1 962 Ala/Pro variant is linked to serum levels of sex steroid and insulin-like growth factor-binding protein 3, providing physiological support for a role of PER1 in hormone-related cancer. 69 …”

Section: Per1mentioning

confidence: 99%

“…23 At a physiological level, the aforementioned 5-repeat allele correlates with higher levels of serum insulin-like growth factor-I (IGF) and the ratio of IGF-I to IGF-binding protein 3, which may contribute to hormone-related cancer. 69 Furthermore, inflammation is an established cancer risk factor and carriers of the 5-repeat allele show elevated levels of the cytokine interleukin-6. 103 …”

Section: Per3mentioning

confidence: 99%

“…23,43 Furthermore, another variant in CK1ε correlates with testosterone to dihydrotestosterone ratio in the serum, which may contribute to the pathology of prostate cancer. 69 …”

Section: Ck1εmentioning

confidence: 99%

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Diversity of Human Clock Genotypes and Consequences

Zhang

Ptáček

2013

Progress in Molecular Biology and Translational Science

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The molecular clock consists of a number of genes that form transcriptional and post-transcriptional feedback loops, which function together to generate circadian oscillations that give rise to circadian rhythms of our behavioral and physiological processes. Genetic variations in these clock genes have been shown to be associated with phenotypic effects in a repertoire of biological processes, such as diurnal preference, sleep, metabolism, mood regulation, addiction, and fertility. Consistently, rodent models carrying mutations in clock genes also demonstrate similar phenotypes. Taken together, these studies suggest that human clock-gene variants contribute to the phenotypic differences observed in various behavioral and physiological processes, although to validate this requires further characterization of the molecular consequences of these polymorphisms. Investigating the diversity of human genotypes and the phenotypic effects of these genetic variations shall advance our understanding of the function of the circadian clock and how we can employ the clock to improve our overall health.

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Section: Npas2mentioning

confidence: 99%

Section: Per1mentioning

confidence: 99%

Section: Per3mentioning

confidence: 99%

“…23,43 Furthermore, another variant in CK1ε correlates with testosterone to dihydrotestosterone ratio in the serum, which may contribute to the pathology of prostate cancer. 69 …”

Section: Ck1εmentioning

confidence: 99%

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Diversity of Human Clock Genotypes and Consequences

Zhang

Ptáček

2013

Progress in Molecular Biology and Translational Science

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“…IGFBP3, may also be influenced by circadian genes. Taken together with findings that variants in circadian genes are associated with delayed sleep phase syndrome and morning/evening preference, it is plausible that variants in these genes are associated with varying serum hormone levels (24).…”

Section: Discussionmentioning

confidence: 95%

Male-female differences in 6-sulfatoxymelatonin excretion in hypopituitary patients

Fideleff

Boquete

et al. 2016

Arch. Endocrinol. Metab.

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Objective: To evaluate melatonin secretion in adult hypopituitary patients with Growth Hormone deficiency (AGHD) on and off replacement therapy. Subjects and methods: We studied 48 subjects: 12 (6 males) untreated AGHD (AGHDnt), 20 (10 males) treated AGHD (AGHDt) and 16 healthy subjects (8 males) as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24 h samples), nocturnal (6-SMn): 1800-0800 and diurnal samples (6-SMd): 0800-1800. Results: Significant differences were observed among the 3 groups of male subjects, in total 6-SM (p < 0.05), nocturnal 6-SM (p < 0.02) and nighttime-daytime delta values (p < 0.003). CG had significantly higher values than the AGHDnt in total 6-SM (p < 0.01), nocturnal 6-SM (p < 0.05) and nighttime-daytime delta values (p < 0.01). AGHDt patients showed significantly higher levels in nighttime-daytime delta values than AGHDnt patients (p < 0.05). In females, no significant differences were found among the 3 groups studied in total, nocturnal, diurnal or nighttime-daytime delta values. In males, significant correlations were found among total 6-SM (r = 0.58; p = 0.029), nocturnal 6-SM (r = 0.70; p = 0.006) and nighttime-daytime delta values (r = 0.71; p = 0.004) vs. serum IGF-1 levels in subjects evaluated. In females, significant correlations were found among total 6-SM (r = 0.57; p = 0.02) vs. serum IGF-1 levels in subjects evaluated. A tendency towards a significant correlation was found in diurnal 6-SM (r = 0.48; p = 0.07). Conclusions: Our findings show a sexual dimorphism in 6-SM excretion in AGHD patients and provide an interesting approach to a further understanding of some chronobiological disorders involved in GH deficiency. Arch Endocrinol Metab. 2016;60(3):223-30

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Circadian genes and breast cancer susceptibility in rotating shift workers

Monsees

Kraft

Hankinson

et al. 2012

Intl Journal of Cancer

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Rotating night shift work is associated with increased risk of breast cancer, likely via circadian disruption. We hypothesized that circadian pathway genes influence breast cancer risk, particularly in rotating night shift workers. We selected 178 common variants across 15 genes pertinent to the circadian system. Using a mixed candidate- and tag-single nucleotide polymorphism approach, we tested for associations between these variants and breast cancer risk in 1,825 women within the Nurses’ Health Study II cohort and investigated potential interactions between genotype and rotating shift-work in a subset of 1,318 women. Multiple-testing-adjusted p-values were obtained by permutation (n=10,000). None of the selected variants was significantly associated with breast cancer risk. However, when accounting for potential effect modification, rs23051560 (Ala394Thr) in the largest circadian gene, Neuronal PAS domain protein 2 (NPAS2) was most strongly associated with breast cancer risk (nominal test for interaction p-value=0.0005; 10,000-permutation-based main-effects p-value among women with <24 months of shift-work=0.003). The observed multiplicative association with breast cancer risk per minor allele (A) was 0.65 (95%CI=0.51–0.82) among women with <24 months of shift-work, and 1.19 (95%CI=0.93–1.54) with ≥24 months of shift-work. Women homozygous for the minor allele (AA) with ≥24 months of shift-work had a 2.83-times higher breast cancer risk compared to homozygous AA women with <24 months of shift-work (95%CI=1.47–5.56). In smmary, common variation in circadian genes plays at most a small role in breast cancer risk among women of European ancestry. The impact of NPAS2 Ala394Thr in the presence of rotating shift-work requires further investigation.

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Correlation between Circadian Gene Variants and Serum Levels of Sex Steroids and Insulin-like Growth Factor-I

Cited by 31 publications

References 37 publications

Diversity of Human Clock Genotypes and Consequences

Diversity of Human Clock Genotypes and Consequences

Male-female differences in 6-sulfatoxymelatonin excretion in hypopituitary patients

Circadian genes and breast cancer susceptibility in rotating shift workers

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