title: Genetic and environmental influences on spontaneous micronuclei frequencies in children and adults: a twin study.
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.
authors.affiliation: Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298-0662, USA.
authors.forename: Kimberly H
authors.initials: KH
authors.lastname: Jones
authors.forename: Timothy P
authors.initials: TP
authors.lastname: York
authors.forename: Jane
authors.initials: J
authors.lastname: Juusola
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferreira-Gonzalez
authors.forename: Hermine H
authors.initials: HH
authors.lastname: Maes
authors.forename: Colleen
authors.initials: C
authors.lastname: Jackson-Cook
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D002648:Child; D005260:Female; D059647:Gene-Environment Interaction; D006262:Health; D006801:Humans; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D008957:Models, Genetic; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D014427:Twins / Q000235:genetics*; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics; D055815:Young Adult