title: Evaluation of how gene-job strain interaction affects blood pressure in the PAMELA study.
abstract: OBJECTIVE
  To see whether there is interaction between single nucleotide polymorphisms (SNPs) belonging to candidate genes for hypertension and job strain and its components (job demand and job control) in an accurately phenotyped Italian cohort (Pressioni Arteriose Monitorate E Loro Associazioni).
  
  
  METHODS
  From the Pressioni Arteriose Monitorate E Loro Associazioni cohort, we sampled 924 employed men and women who had completed a modified version of the Karasek questionnaire and for whom deoxyribonucleic acid information was available. We selected 1,510 common tagging and putative functional SNPs in 92 candidate autosomal genes involved in sympathetic nervous system, oxidative stress, renin-angiotensin-aldosterone system, and sodium balance. The interaction of each candidate SNP with the perceived job stress scores on ambulatory systolic and diastolic blood pressures was evaluated by adding product terms to a multiple regression linear model, adjusted for sex, age, total cholesterol, and body mass index.
  
  
  RESULTS
  Among all the SNPs tested, the interaction of SNP rs11210278 located on the endothelin 2 gene and job control was statistically significant after controlling for multiple testing, using false discovery rate (unadjusted p = .00000661; p adjusted for false discovery rate = .0085), indicating an inverse association with systolic blood pressure for the homozygous wild-type allele (C/C) and a positive association for the variant genotypes (C/T and T/T).
  
  
  CONCLUSIONS
  We show that the hypertensive response to job strain is present only in carriers of the rs11210278 wild-type genotype. The phenomenon is discussed in relationship to the controversial results of field studies on job strain and hypertension.
authors.affiliation: Department of Statistics, University of Milano-Bicocca, Milano, Via Bicocca degli Arcimboldi 8, 20126 Milano, Italy. cristinamenni@gmail.com
authors.forename: Cristina
authors.initials: C
authors.lastname: Menni
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bagnardi
authors.forename: Sandosh
authors.initials: S
authors.lastname: Padmanabhan
authors.forename: Rita
authors.initials: R
authors.lastname: Facchetti
authors.forename: Roberto
authors.initials: R
authors.lastname: Sega
authors.forename: Marco M
authors.initials: MM
authors.lastname: Ferrario
authors.forename: Paolo
authors.initials: P
authors.lastname: Brambilla
authors.forename: Wai K
authors.initials: WK
authors.lastname: Lee
authors.forename: Anna F
authors.initials: AF
authors.lastname: Dominiczak
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Cesana
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000235:genetics; D018660:Blood Pressure Monitoring, Ambulatory; D015992:Body Mass Index; D015331:Cohort Studies; D019333:Endothelin-2 / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D007558:Italy; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012084:Renin-Angiotensin System / Q000235:genetics; D012307:Risk Factors; D013315:Stress, Psychological / Q000453:epidemiology / Q000503:physiopathology* / Q000523:psychology; D011795:Surveys and Questionnaires; D016526:Workload / Q000523:psychology* / Q000706:statistics & numerical data
chemical_list: D019333:Endothelin-2