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遗传和环境因素对儿童和成人自发微核频率的影响:一项双胞胎研究。

Genetic and environmental influences on spontaneous micronuclei frequencies in children and adults: a twin study.

机构信息

Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298-0662, USA.

出版信息

Mutagenesis. 2011 Nov;26(6):745-52. doi: 10.1093/mutage/ger042. Epub 2011 Jul 15.

Abstract

The primary aim of this study was to quantify genetic and environmental influences on the frequency of spontaneously occurring micronuclei in children and adults. To meet this aim, a total of 63 male and female twin pairs and 19 singletons (145 individuals) were evaluated, ranging in age from 7 to 85 years. Micronuclei frequencies significantly increased with age for both genders (r = 0.49, P < 0.001), with the lowest and highest rates being seen in the 7- to 9 (mean = 0.56%, SD = .28) and 60- to 69-year-olds (mean = 2.12%, SD = 1.0), respectively. This age effect was significantly more pronounced in females than males (P = 0.017). In addition to the main effect of age, the completion of puberty in either gender (P = 0.036) and menopause in females (P = 0.024) was associated with a significant increase in micronuclei frequencies. Genetic model fitting indicated that influences from both additive genetic (65.2% of variance) and unique environmental (34.8% of variance) sources best explained the observed micronuclei frequencies in monozygotic and dizygotic twin pairs. Self-reported health conditions associated with an increased frequency of micronuclei included a history of allergies (P < 0.007) and migraines (P = 0.026). Multivitamin use was also associated with increased micronuclei frequencies (P = 0.004). In contrast, significantly lower micronuclei frequencies were associated with arthritis (P = 0.002), as well as consuming fruit (P = 0.014), green, leafy vegetables (P < 0.001) and/or folate-enriched bread (P = 0.035). A sex-specific effect, resulting in a significantly increased frequency of micronuclei with tobacco usage, was observed for females (but not males). Gender differences also moderated the impact of vitamin D and calcium consumption. In conclusion, the frequency of spontaneously arising micronuclei in humans is a complex trait, being influenced by both heritable genetic and environmental components. Recognition of factors contributing to baseline levels of micronuclei should provide guidance to researchers in designing studies to evaluate agents hypothesised to influence chromosomal instability.

摘要

本研究的主要目的是量化遗传和环境因素对儿童和成人自发微核频率的影响。为了达到这个目的,总共评估了 63 对男性和女性双胞胎和 19 个单胎(145 人),年龄从 7 岁到 85 岁。两性的微核频率均随年龄增长而显著增加(r = 0.49,P < 0.001),最低和最高发生率分别见于 7-9 岁(均值 = 0.56%,SD =.28)和 60-69 岁(均值 = 2.12%,SD = 1.0)。这种年龄效应在女性中比男性更为显著(P = 0.017)。除了年龄的主要影响外,两性的青春期完成(P = 0.036)和女性的更年期(P = 0.024)与微核频率的显著增加有关。遗传模型拟合表明,来自加性遗传(方差的 65.2%)和独特环境(方差的 34.8%)的影响最好地解释了同卵和异卵双胞胎中观察到的微核频率。与微核频率增加相关的自我报告健康状况包括过敏史(P < 0.007)和偏头痛(P = 0.026)。多维元素的使用也与微核频率增加有关(P = 0.004)。相反,关节炎(P = 0.002)、食用水果(P = 0.014)、绿叶蔬菜(P < 0.001)和/或富含叶酸的面包(P = 0.035)与微核频率显著降低有关。对于女性(而不是男性),观察到了一个性别特异性的影响,即吸烟会导致微核频率显著增加。性别差异也调节了维生素 D 和钙的摄入的影响。总之,人类自发产生的微核频率是一个复杂的特征,受到遗传和环境因素的共同影响。认识到导致微核基线水平的因素应该为研究人员设计评估假设影响染色体不稳定性的药物的研究提供指导。

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