ABSTRACT
The super-sensitivity of the neurohormone melatonin to light in patients with bipolar disorder provides evidence of the circadian nature of the disorder. This response has been proposed as an endophenotype for identifying people at risk of the disorder and guiding investigations of molecular genetic targets. However, before this response is used as an endophenotypic marker, the heritable nature of melatonin sensitivity in the normal population must be established. The aim of this study was to investigate the heritability of nocturnal melatonin secretion and sensitivity to light in monozygotic and dizygotic twins with no psychiatric history. This study investigated overall melatonin levels (between 2000 and 2400 h) and suppression by 500 lx of light (between 2400 and 0100 h) in 20 pairs of twins (nine monozygotic, 11 dizygotic). The results indicate that melatonin secretion is highly heritable with secretion in one twin being a significant predictor of secretion in their twin in both monozygotic and dizygotic pairs. In relation to light sensitivity, genetic loading appears to play a significant role with the greatest concordance between monozygotic twins, followed by dizygotic twins and finally low concordance in unrelated individuals. This provides additional support for the usefulness of melatonin sensitivity to light as a potential endophenotypic marker of bipolar affective disorder.
Subject(s)
Circadian Rhythm/physiology , Down-Regulation/radiation effects , Melatonin/blood , Melatonin/metabolism , Twins, Dizygotic/blood , Twins, Monozygotic/blood , Adolescent , Adult , Area Under Curve , Bipolar Disorder/diagnosis , Bipolar Disorder/genetics , Bipolar Disorder/physiopathology , Circadian Rhythm/genetics , Circadian Rhythm/radiation effects , Darkness , Down-Regulation/genetics , Down-Regulation/physiology , Female , Genetic Load , Humans , Light , Male , Melatonin/radiation effects , Pineal Gland/metabolism , Pineal Gland/radiation effects , Quantitative Trait, Heritable , Statistics, Nonparametric , Twins, Dizygotic/genetics , Twins, Monozygotic/geneticsABSTRACT
BACKGROUND/AIMS: There are limited data on the frequency and biochemical expression of the haemochromatosis-associated mutations C282Y and H63D in healthy people. METHODS: We genotyped (bi-directional PCR amplification of specific alleles method) and performed serum iron studies in randomly selected English male blood donors (<4 previous units donated) in four age bands <30, 30-40, 40-50 and >50 years. RESULTS: In 6261 subjects, frequency of C282Y homozygosity (+/+) was 0.3%, C282Y/H63D compound heterozygosity (+/-) 2.0%, and H63D and C282Y heterozygosity +/-, 21.7 and 10.4%, respectively. Genotype distribution was within Hardy-Weinberg equilibrium in each age band. C282Y +/- frequency fell from 11.7% in subjects <30 years to 8.2% in subjects >50 (Chi2 7.19; P<0.005). No such trend was seen for C282Y +/+. In C282Y +/+ subjects, median serum ferritin was 247 (range 60-2449) microg/l and exceeded >500 microg/l in only two of 18 subjects. Compared to wild/wild (-/-) subjects, C282Y and H63D +/- subjects had slightly higher serum iron and lower unsaturated iron binding concentrations, similar overall serum ferritin values but higher serum ferritin values in subjects who had previously donated blood. CONCLUSIONS: C282Y +/+ shows limited biochemical expression and no trend towards age-related attrition. C282Y and H63D +/- may protect against iron deficiency.
