Neuregulin-1 Genotype Moderates the Association Between Job Strain and Early Atherosclerosis in Young Men Mirka Hintsanen, Ph.D. Department of Psychology, University of Helsinki, Finland Marko Elovainio, Ph.D. Department of Psychology, University of Helsinki, Finland, and National Research and Development Centre for Welfare and Health, Finland Sampsa Puttonen, Ph.D. Department of Psychology, University of Helsinki, Finland Mika Kivima ¨ki, Ph.D. Department of Psychology, University of Helsinki, Finland, and International Centre for Health and Society, Department of Epidemiology and Public Health, University College London, UK Olli T. Raitakari, M.D., Ph.D. Department of Clinical Physiology, University of Turku, Finland Terho Lehtima ¨ki, M.D., Ph.D. and Riika Rontu, Ph.D. Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, the Medical School University of Tampere and Centre for Laboratory Medicine, Tampere University Hospital, Finland Markus Juonala M.D., Ph.D. Research Centre of Applied and Preventive Cardiovascular Medicine University of Turku, Finland Mika Ka ¨ho ¨nen, M.D., Ph.D. Department of Clinical Physiology, Tampere University Hospital, Finland Jorma Viikari, M.D., Ph.D. Department of Medicine, University of Turku, Finland Liisa Keltikangas-Ja ¨rvinen, Ph.D. Department of Psychology, University of Helsinki, Finland ABSTRACT Background: Although it is known that a given level of strain does not induce a corresponding CHD risk in all indi- viduals, factors that predict groups at risk have remained unclear. Neuregulin-1 (NRG-1) has various roles in the development and function of the heart and autonomic nervous system. Purpose: We examined whether polymorphic vari- ation in NRG-1 moderates the association between job strain and early atherosclerosis. Methods: The participants (M age ¼ 32.5) were 349 women and 357 men derived from the population-based Cardiovascular Risk in Young Finns study. Job strain was defined as the joint effect of job demands and job control. Preclinical atherosclerosis was measured using carotid intima-media thickness (IMT) ultrasound. Results: NRG-1 single nucleotide polymorphism SNP8NRG221533 (T to C) was found to moderate the association between job strain and IMT in men (p ¼ .04). Job strain was significantly associated with increased IMT among men with T=T genotype but not among the others. A direct association between NRG-1 and IMT was found in women. Conclusions: Our results suggest that the effect of job strain on early atherosclerosis is dependent on NRG-1 genotype in men. Gene  Environment Interaction approach seems to offer important additional information in stress research. (Ann Behav Med 2007, 33(2):148–155) INTRODUCTION The job demand-control model by Karasek (1) is one of the most widely tested conceptual models concerning psychosocial work environment and its relations to coron- ary heart disease (CHD) (for a review see 2). The model specifies two independent inputs influencing strain: job This study was supported by Academy of Finland (Grants 111056, 209514, and 209518 for L.K.-J., 104891 and 105195 for M.K., 53392 and 15486 for O.T.R), the Emil Aaltonen Foundation (L.K.-J. and T.L.), the Psykonet Graduate School of Psychology (M.H.), and The Finnish Foundation of Cardiovascular Research (O.T.R). Reprint Address: L. Keltikangas-Ja ¨rvinen, Siltavuorenpenger 20 D (P.O. Box 9), 00014 University of Helsinki, Finland. E-mail: liisa.keltikangas-jarvinen@helsinki.fi # 2007 by The Society of Behavioral Medicine. 148