title: Individual multi-locus heterozygosity is associated with lower morning plasma cortisol concentrations.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.
authors: Lina
authors: L
authors: Zgaga
authors: Veronique
authors: V
authors: Vitart
authors: Caroline
authors: C
authors: Hayward
authors: Darko
authors: D
authors: Kastelan
authors: Ozren
authors: O
authors: Polasek
authors: Miro
authors: M
authors: Jakovljevic
authors: Ivana
authors: I
authors: Kolcic
authors: Zrinka
authors: Z
authors: Biloglav
authors: Alan F
authors: AF
authors: Wright
authors: Harry
authors: H
authors: Campbell
authors: Brian R
authors: BR
authors: Walker
authors: Igor
authors: I
authors: Rudan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002940:Circadian Rhythm; D017523:Croatia; D004247:DNA / Q000097:blood / Q000302:isolation & purification; D004522:Educational Status; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D012737:Sex Factors; D012959:Socioeconomic Factors; D013315:Stress, Psychological / Q000097:blood* / Q000150:complications; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D004247:DNA; D006854:Hydrocortisone