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The Association of Neighborhood Gene-Environment Susceptibility with Cortisol and Blood Pressure in African-American Adults

  • Original Article
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Annals of Behavioral Medicine

Abstract

Background

African-American adults are disproportionately affected by stress-related chronic conditions like high blood pressure (BP), and both environmental stress and genetic risk may play a role in its development.

Purpose

This study tested whether the dual risk of low neighborhood socioeconomic status (SES) and glucocorticoid genetic sensitivity interacted to predict waking cortisol and BP.

Methods

Cross-sectional waking cortisol and BP were collected from 208 African-American adults who were participating in a follow-up visit as part of the Positive Action for Today’s Health trial. Three single-nucleotide polymorphisms were genotyped, salivary cortisol samples were collected, and neighborhood SES was calculated using 2010 Census data.

Results

The sample was mostly female (65 %), with weight classified as overweight or obese (M BMI = 32.74, SD = 8.88) and a mean age of 55.64 (SD = 15.21). The gene-by-neighborhood SES interaction predicted cortisol (B = 0.235, p = .001, r 2 = .036), but not BP. For adults with high genetic sensitivity, waking cortisol was lower with lower SES but higher with higher SES (B = 0.87). Lower neighborhood SES was also related to higher systolic BP (B = −0.794, p = .028).

Conclusions

Findings demonstrated an interaction whereby African-American adults with high genetic sensitivity had high levels of waking cortisol with higher neighborhood SES, and low levels with lower neighborhood SES. This moderation effect is consistent with a differential susceptibility gene-environment pattern, rather than a dual-risk pattern. These findings contribute to a growing body of evidence that demonstrates the importance of investigating complex gene-environment relations in order to better understand stress-related health disparities.

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References

  1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2014 update: A report from the American Heart Association. Circulation. 2014; 129: e28-e292.

    Article  PubMed  Google Scholar 

  2. Havranek EP, Mujahid MS, Barr DA, et al. Social determinants of risk and outcomes for cardiovascular disease: A scientific statement from the American heart association. Circulation. 2015. Advance online publication. PMCID: 26240271.

  3. Mensah GA, Mokdad AH, Ford ES, Greenlund KJ, Croft JB. State of disparities in cardiovascular health in the United States. Circulation. 2005; 111: 1233-1241.

    Article  PubMed  Google Scholar 

  4. Cutler J, Sorlie P, Wolz M, et al. Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988–1994 and 1999–2004. Hypertension. 2008; 52: 818-827.

    Article  CAS  PubMed  Google Scholar 

  5. Gadegbeku C, Lea J, Jamerson K. Update on disparities in the pathophysiology and management of hypertension: Focus on African Americans. Med Clin North Am. 2005; 89: 921-933. 930.

    Article  PubMed  Google Scholar 

  6. Yoon SS, Ostchega Y, Louis T. Recent trends in the prevalence of high blood pressure and its treatment and control, 1999–2008. NCHS Data Brief. 2010;1–8.

  7. Johnson KW, Anderson NB, Bastida E, et al. Macrosocial and environmental influences on minority health. Health Psychol. 1995; 14: 601-612.

    Article  CAS  PubMed  Google Scholar 

  8. Dulin-Keita A, Casazza K, Fernandez JR, Goran MI, Gower B. Do neighbourhoods matter? Neighbourhood disorder and long-term trends in serum cortisol levels. J Epidemiol Community Health. 2012; 66: 24-29.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Matthews KA, Gallo LC. Psychological perspectives on pathways linking socioeconomic status and physical health. Annu Rev Psychol. 2011; 62: 501-530.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Kuzawa C, Sweet E. Epigenetics and the embodiment of race: Developmental origins of US racial disparities in cardiovascular health. Am J Hum Biol. 2009; 21: 2-15.

    Article  PubMed  Google Scholar 

  11. Rankinen T, Sarzynski MA, Ghosh S, Bouchard C. Are there genetic paths common to obesity, cardiovascular disease outcomes, and cardiovascular risk factors? Circ Res. 2015; 116: 909-922.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Imumorin I, Dong Y, Zhu H, et al. A gene-environment interaction model of stress-induced hypertension. Cardiovasc Toxicol. 2005; 5: 109-132.

    Article  CAS  PubMed  Google Scholar 

  13. Zhao Q, Kelly TN, Li C, He J. Progress and future aspects in genetics of human hypertension. Curr Hypertens Rep. 2013; 15: 676-686.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Dick DM, Agrawal A, Keller MC, et al. Candidate gene-environment interaction research: Reflections and recommendations. Perspect Psychol Sci. 2015; 10: 37-59.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Shanahan MJ, Hofer SM. Social context in gene-environment interactions: Retrospect and prospect. J Gerontol B Psychol Sci Soc Sci. 2005; 60(Spec No 1): 65-76.

    Article  PubMed  Google Scholar 

  16. Shavers VL. Measurement of socioeconomic status in health disparities research. J Natl Med Assoc. 2007; 99: 1013-1023.

    PubMed Central  PubMed  Google Scholar 

  17. Wilson DK, Kirtland KA, Ainsworth BE, Addy CL. Socioeconomic status and perceptions of access and safety for physical activity. Ann Behav Med. 2004; 28: 20-28.

    Article  PubMed  Google Scholar 

  18. Morenoff J, House J, Hansen B, et al. Understanding social disparities in hypertension prevalence, awareness, treatment, and control: The role of neighborhood context. Soc Sci Med. 2007; 65: 1853-1866.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Thomas K, Nelesen R, Ziegler M, Natarajan L, Dimsdale J. Influence of education and neighborhood poverty on pressor responses to phenylephrine in African-Americans and Caucasian-Americans. Biol Psychol. 2009; 82: 18-24.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Thorpe R Jr, Brandon D, LaVeist T. Social context as an explanation for race disparities in hypertension: Findings from the Exploring Health Disparities in Integrated Communities (EHDIC) Study. Soc Sci Med. 2008; 67: 1604-1611.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Diez Roux AV, Chambless L, Merkin SS, et al. Socioeconomic disadvantage and change in blood pressure associated with aging. Circulation. 2002; 106: 703-710.

    Article  PubMed  Google Scholar 

  22. Kapuku G, Treiber FA, Davis HC. Relationships among socioeconomic status, stress induced changes in cortisol, and blood pressure in African American males. Ann Behav Med. 2002; 24: 320-325.

    Article  PubMed  Google Scholar 

  23. Anderson NB, Armstead CA. Toward understanding the association of socioeconomic status and health: A new challenge for the biopsychosocial approach. Psychosom Med. 1995; 57: 213-225.

    Article  CAS  PubMed  Google Scholar 

  24. Anderson NB, Nickerson KJ. Genes, race, and psychology in the genome era: An introduction. Am Psychol. 2005; 60: 5-8.

    Article  PubMed  Google Scholar 

  25. Constanti A. Basic Endocrinology for Students of Pharmacy and Allied Health Sciences. CRC Press; 1998.

  26. Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 1: Outcomes. Nat Rev Endocrinol. 2014; 10: 391-402.

    Article  CAS  PubMed  Google Scholar 

  27. Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 2: Mechanisms. Nat Rev Endocrinol. 2014; 10: 403-411.

    Article  CAS  PubMed  Google Scholar 

  28. Whitworth J, Williamson P, Mangos G, Kelly J. Cardiovascular consequences of cortisol excess. Vasc Health Risk Manag. 2005; 1: 291.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Belsky J, Pluess M. Beyond diathesis stress: Differential susceptibility to environmental influences. Psychol Bull. 2009; 135: 885-908.

    Article  PubMed  Google Scholar 

  30. Belsky J, Pluess M. Beyond risk, resilience, and dysregulation: Phenotypic plasticity and human development. Dev Psychopathol. 2013; 25: 1243-1261.

    Article  PubMed  Google Scholar 

  31. Wust S, van Rossum E, Federenko I, et al. Common polymorphisms in the glucocorticoid receptor gene are associated with adrenocortical responses to psychosocial stress. J Clin Endocrinol Metab. 2004; 89: 565.

    Article  PubMed  Google Scholar 

  32. Petersen K, Bleil M, McCaffery J, et al. Community socioeconomic status is associated with carotid artery atherosclerosis in untreated, hypertensive men. Am J Hypertens. 2006; 19: 560-566.

    Article  PubMed  Google Scholar 

  33. Jones-Webb R, Yu X, O'Brien J, et al. Does socioeconomic position moderate the effects of race on cardiovascular disease mortality? Ethn Dis. 2004; 14: 489-496.

    PubMed  Google Scholar 

  34. Cubbin C, Hadden WC, Winkleby MA. Neighborhood context and cardiovascular disease risk factors: The contribution of material deprivation. Ethn Dis. 2001; 11: 687-700.

    CAS  PubMed  Google Scholar 

  35. Hajat A, Moore K, Phuong Do D, et al. Examining the cross-sectional and longitudinal association between diurnal cortisol and neighborhood characteristics: Evidence from the multi-ethnic study of atherosclerosis. Health Place. 2015; 34: 199-206.

    Article  PubMed  Google Scholar 

  36. Cohen S, Doyle W, Baum A. Socioeconomic status is associated with stress hormones. Psychosom Med. 2006; 68: 414-420.

    Article  PubMed  Google Scholar 

  37. Bennett GG, Merritt MM, Wolin KY. Ethnicity, education, and the cortisol response to awakening: A preliminary investigation. Ethn Health. 2004; 9: 337-347.

    Article  PubMed  Google Scholar 

  38. Barrington WE, Stafford M, Hamer M, et al. Neighborhood socioeconomic deprivation, perceived neighborhood factors, and cortisol responses to induced stress among healthy adults. Health Place. 2014; 27: 120-126.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Rudolph KE, Gary SW, Stuart EA, et al. The association between cortisol and neighborhood disadvantage in a U.S. population-based sample of adolescents. Health Place. 2014; 25: 68-77.

    Article  PubMed Central  PubMed  Google Scholar 

  40. Manenschijn L, van den Akker E, Lamberts S, van Rossum E. Clinical features associated with glucocorticoid receptor polymorphisms. Ann N Y Acad Sci. 2009; 1179: 179-198.

    Article  CAS  PubMed  Google Scholar 

  41. DeRijk R, de Kloet E. Corticosteroid receptor genetic polymorphisms and stress responsivity. Endocrine. 2005; 28: 263-269.

    Article  CAS  PubMed  Google Scholar 

  42. Lian Y, Xiao J, Wang Q, et al. The relationship between glucocorticoid receptor polymorphisms, stressful life events, social support, and post-traumatic stress disorder. BMC Psychiatry. 2014; 14: 232.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Watt G, Harrap S, Foy C, et al. Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: A four-corners approach to the identification of genetic determinants of blood pressure. J Hypertens. 1992; 10: 473.

    Article  CAS  PubMed  Google Scholar 

  44. Stevens A, Ray D, Zeggini E, et al. Glucocorticoid sensitivity is determined by a specific glucocorticoid receptor haplotype. J Clin Endocrinol Metab. 2004; 89: 892.

    Article  CAS  PubMed  Google Scholar 

  45. Kumsta R, Entringer S, Koper J, et al. Sex specific associations between common glucocorticoid receptor gene variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress. Biol Psychiatry. 2007; 62: 863-869.

    Article  CAS  PubMed  Google Scholar 

  46. Kirchheiner J, Lorch R, Lebedeva E, et al. Genetic variants in FKBP5 affecting response to antidepressant drug treatment. Pharmacogenomics. 2008; 9: 841-846.

    Article  CAS  PubMed  Google Scholar 

  47. Binder EB, Bradley RG, Liu W, et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA. 2008; 299: 1291-1305.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Buchmann AF, Holz N, Boecker R, et al. Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood. Eur Neuropsychopharmacol. 2014; 24: 837-845.

    Article  CAS  PubMed  Google Scholar 

  49. Lessard J, Holman EA. FKBP5 and CRHR1 polymorphisms moderate the stress-physical health association in a national sample. Health Psychol. 2014; 33: 1046-1056.

    Article  PubMed  Google Scholar 

  50. Chung CC, Shimmin L, Natarajan S, et al. Glucocorticoid receptor gene variant in the 3′ untranslated region is associated with multiple measures of blood pressure. J Clin Endocrinol Metab. 2009; 94: 268-276.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Kumsta R, Moser D, Streit F, et al. Characterization of a glucocorticoid receptor gene (GR, NR3C1) promoter polymorphism reveals functionality and extends a haplotype with putative clinical relevance. Am J Med Genet B Neuropsychiatr Genet. 2009; 150: 476-482.

    Article  Google Scholar 

  52. Geelhoed JJ, van Duijn C, van Osch-Gevers L, et al. Glucocorticoid receptor-9beta polymorphism is associated with systolic blood pressure and heart growth during early childhood. The Generation R Study. Early Hum Dev. 2011; 87: 97-102.

    Article  CAS  PubMed  Google Scholar 

  53. Coulon SM, Wilson DK, Griffin S, et al. Formative process evaluation for implementing a social marketing intervention to increase walking among African Americans in the positive action for today's health trial. Am J Public Health. 2012; 102: 2315-2321.

    Article  PubMed Central  PubMed  Google Scholar 

  54. Wilson DK, Van Horn ML, Siceloff ER, et al. The Results of the “Positive Action for Today's Health” (PATH) trial for increasing walking and physical activity in underserved African-American Communities. Ann Behav Med. 2015; 49: 398-410.

    Article  PubMed Central  PubMed  Google Scholar 

  55. U.S. Census Bureau: 2010 Census Constituent FAQs. 2010.

  56. Diez-Roux AV, Kiefe CI, Jacobs DR Jr, et al. Area characteristics and individual-level socioeconomic position indicators in three population-based epidemiologic studies. Ann Epidemiol. 2001; 11: 395-405.

    Article  CAS  PubMed  Google Scholar 

  57. Wickrama KK, O'Neal CW, Lee TK. Early community context, genes, and youth body mass index trajectories: An investigation of gene-community interplay over early life course. J Adolesc Health. 2013; 53: 328-334.

    Article  PubMed  Google Scholar 

  58. Genomes Project C, Abecasis GR, Altshuler D, et al. A map of human genome variation from population-scale sequencing. Nature. 2010; 467: 1061-1073.

    Article  Google Scholar 

  59. Levine A, Zagoory-Sharon O, Feldman R, Lewis J, Weller A. Measuring cortisol in human psychobiological studies. Physiol Behav. 2007; 90: 43-53.

    Article  CAS  PubMed  Google Scholar 

  60. Dockray S, Bhattacharyya MR, Molloy GJ, Steptoe A. The cortisol awakening response in relation to objective and subjective measures of waking in the morning. Psychoneuroendocrinology. 2008; 33: 77-82.

    Article  CAS  PubMed  Google Scholar 

  61. Hackman DA, Betancourt LM, Brodsky NL, Hurt H, Farah MJ. Neighborhood disadvantage and adolescent stress reactivity. Front Hum Neurosci. 2012; 6: 277.

    Article  PubMed Central  PubMed  Google Scholar 

  62. Vreeburg SA, Kruijtzer BP, van Pelt J, et al. Associations between sociodemographic, sampling and health factors and various salivary cortisol indicators in a large sample without psychopathology. Psychoneuroendocrinology. 2009; 34: 1109-1120.

    Article  CAS  PubMed  Google Scholar 

  63. Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: A working group report from the National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. Pediatrics. 1996; 98:649–658.

  64. Calhoun D, Jones D, Textor S, et al. Resistant hypertension: Diagnosis, evaluation, and treatment: A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008; 117: e510.

    Article  PubMed  Google Scholar 

  65. Enders C, Bandalos D. The relative performance of full information maximum likelihood estimation for missing data in structural equation models. Struct Equ Model. 2001; 8: 430-457.

    Article  Google Scholar 

  66. Acock AC. Working with missing values. J Marriage Fam. 2005; 67: 1012-1028.

    Article  Google Scholar 

  67. Krabbendam L, van Os J. Schizophrenia and urbanicity: A major environmental influence--conditional on genetic risk. Schizophr Bull. 2005; 31: 795-799.

    Article  PubMed  Google Scholar 

  68. Klengel T, Mehta D, Anacker C, et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci. 2013; 16: 33-41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Menke A, Klengel T, Rubel J, et al. Genetic variation in FKBP5 associated with the extent of stress hormone dysregulation in major depression. Genes Brain Behav. 2013; 12: 289-296.

    Article  CAS  PubMed  Google Scholar 

  70. Suderman M, McGowan PO, Sasaki A, et al. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus. Proc Natl Acad Sci U S A. 2012; 109(Suppl 2): 17266-17272.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Velders FP, Dieleman G, Cents RA, et al. Variation in the glucocorticoid receptor gene at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child cortisol reactivity and behavior. Neuropsychopharmacology. 2012; 37: 2541-2549.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Barnes JC, Jacobs BA. Genetic risk for violent behavior and environmental exposure to disadvantage and violent crime: The case for gene-environment interaction. J Interpers Violence. 2013; 28: 92-120.

    Article  CAS  PubMed  Google Scholar 

  73. Bolten M, Nast I, Skrundz M, et al. Prenatal programming of emotion regulation: Neonatal reactivity as a differential susceptibility factor moderating the outcome of prenatal cortisol levels. J Psychosom Res. 2013; 75: 351-357.

    Article  PubMed  Google Scholar 

  74. Groeneveld MG, Vermeer HJ, van IJzendoorn IMH, Linting M. Stress, cortisol and well-being of caregivers and children in home-based child care: A case for differential susceptibility. Child Care Health Dev. 2012; 38: 251-260.

    Article  CAS  PubMed  Google Scholar 

  75. Reiner AP, Ziv E, Lind DL, et al. Population structure, admixture, and aging-related phenotypes in African American adults: The Cardiovascular Health Study. Am J Hum Genet. 2005; 76: 463-477.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Chen E, Paterson L. Neighborhood, family, and subjective socioeconomic status: How do they relate to adolescent health? Health Psychol. 2006; 25: 704-714.

    Article  CAS  PubMed  Google Scholar 

  77. Ranjit N, Young EA, Kaplan GA. Material hardship alters the diurnal rhythm of salivary cortisol. Int J Epidemiol. 2005; 34: 1138-1143.

    Article  PubMed  Google Scholar 

  78. Almeida DM, Piazza JR, Stawski RS. Interindividual differences and intraindividual variability in the cortisol awakening response: An examination of age and gender. Psychol Aging. 2009; 24: 819-827.

    Article  PubMed Central  PubMed  Google Scholar 

  79. Skinner ML, Shirtcliff EA, Haggerty KP, Coe CL, Catalano RF. Allostasis model facilitates understanding race differences in the diurnal cortisol rhythm. Dev Psychopathol. 2011; 23: 1167-1186.

    Article  PubMed Central  PubMed  Google Scholar 

  80. Knight JM, Avery EF, Janssen I, Powell LH. Cortisol and depressive symptoms in a population-based cohort of midlife women. Psychosom Med. 2010; 72: 855-861.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Polk DE, Cohen S, Doyle WJ, Skoner DP, Kirschbaum C. State and trait affect as predictors of salivary cortisol in healthy adults. Psychoneuroendocrinology. 2005; 30: 261-272.

    Article  CAS  PubMed  Google Scholar 

  82. Adler NE, Newman K. Socioeconomic disparities in health: pathways and policies. Health Aff (Millwood). 2002; 21: 60-76.

    Article  Google Scholar 

  83. Koh HK. A 2020 vision for healthy people. N Engl J Med. 2010; 362: 1653-1656.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a grant from the National Institute of Diabetes, Digestive, and Kidney Diseases and the National Institute of Child Health and Human Development to Dawn K. Wilson, Ph.D. (R01 DK067615; R01HD072153), and in part by training grants from the National Institute on Aging (F31 AG039930) and the National Institute of General Medical Sciences (T32 GM081740) to Sandra M. Coulon, Ph.D.

Conflict of Interest and Adherence to Ethical Standards

Sandra M. Coulon, Dawn K. Wilson, M. L. Van Horn, Gregory A. Hand, and Stephen Kresovich declare that they have no conflict of interest. The research was conducted in accordance with ethical standards outlined by the University of South Carolina’s Institutional Review Board. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Authors and Affiliations

  1. Department of Psychology, University of South Carolina, Barnwell College, Columbia, SC, 29201, USA

    Sandra M. Coulon Ph.D. & Dawn K. Wilson Ph.D.

  2. Educational Psychology, University of New Mexico, Albuquerque, NM, 87131, USA

    M. L. Van Horn Ph.D.

  3. School of Public Health, West Virginia University, Morgantown, WV, 26506, USA

    Gregory A. Hand Ph.D., M.P.H.

  4. Genetics and Biochemistry, Clemson University, Clemson, SC, 29634, USA

    Stephen Kresovich Ph.D.

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  1. Sandra M. Coulon Ph.D.
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  3. M. L. Van Horn Ph.D.
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Correspondence to Sandra M. Coulon Ph.D..

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Coulon, S.M., Wilson, D.K., Van Horn, M.L. et al. The Association of Neighborhood Gene-Environment Susceptibility with Cortisol and Blood Pressure in African-American Adults. ann. behav. med. 50, 98–107 (2016). https://doi.org/10.1007/s12160-015-9737-9

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