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Eur J Endocrinol. 2013 Jun 7;169(1):59-64. doi: 10.1530/EJE-12-0916. Print 2013 Jul.

Individual multi-locus heterozygosity is associated with lower morning plasma cortisol concentrations.

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Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.



Stress is implicated as a risk factor for numerous illnesses in humans, putatively in part mediated by biological responses to stress, such as elevated cortisol concentrations. The theory of genetic homoeostasis suggests that individual heterozygosity facilitates compensation for environmental stresses. We hypothesized that heterozygosity ameliorates the biological response to a given level of perceived stress, reflected in lower plasma cortisol concentrations.


We examined the role of heterozygosity in the association between perceived psychological stress and morning cortisol concentrations in 854 individuals from the isolated island of Vis, Croatia.


Cortisol concentrations were measured in morning plasma samples. A total of 1184 autosomal microsatellite markers were genotyped and individual multi-locus heterozygosity (MLH) was calculated as the proportion of heterozygous markers. The General Health Questionnaire with 30 items (GHQ-30) was used to assess the degree of psychological distress.


MEAN MLH WAS 34.850.45% (RANGE: 31.97-36.22%). Psychological distress (GHQ Likert score >31) was more prevalent in women (37 vs 18% in men, P<0.0001), in less educated people (β=-0.35 per year in school, P<0.001) and in lower socio-economic classes (β=-3.59, P<0.0001). Cortisol concentrations were positively associated with psychological distress (β=2.20, P=0.01). In a regression model adjusted for age, BMI, education and GHQ-30 score, MLH was independently and inversely associated with morning plasma cortisol concentrations (P=0.005).


More heterozygous individuals, as measured by microsatellite markers, had lower morning plasma cortisol concentrations for a given level of perceived psychological stress. This may be important, as higher cortisol concentrations may increase the allostatic load and be associated with a higher risk of stress-related illness.

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