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Anita R. Webb, PhD JPS Health Network Fort Worth, Texas

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Presentation on theme: "Anita R. Webb, PhD JPS Health Network Fort Worth, Texas"— Presentation transcript:

1 Anita R. Webb, PhD JPS Health Network Fort Worth, Texas

2 Goals/Objectives  Preview a relatively new field of genetics.  Explore effects of environmental factors on gene expression.  Review examples of research in this arena.  Consider implications for family physicians.

3 Main Points  Environmental factors can affect gene expression.  The environment, including the social environment, can ultimately determine genetic profiles.  New explanations are emerging for chronic medical problems.

4 PREMISE  “It has become increasingly clear that social factors can play a significant role in regulating the activity of human genes.”  Cole, SW. Social regulation of human gene expression. Curr Dir Psychol Sci. 2009; 18(3): 132–137.

5 BASICS  Cells are highly selective about which genes they express.  The expression of a specific gene is often more an exception than the rule.  The social world influences which genes are transcribed within the nuclei of our cells.  Ibid.

6 For Example  “Social stress and isolation have long been known to affect the onset and progression of disease.”  Especially viral infections  Social factors have been linked to  Rhinoviruses  AIDS virus  Several cancer-related viruses  Ibid.

7 Classic Study  Medical students’ health in reaction to course exams  More “colds” preceding exams.  Sheldon Cohen, Ph.D., David A.J. Tyrrell, M.D., and Andrew P. Smith, Ph.D. Psychological stress and susceptibility to the common cold. N Eng J Med. 1991; 325:606-612.

8 Social Regulation of Gene Expression  “Several studies have shown that social influences can penetrate remarkably deeply into our bodies.”  “Key immune system genes are also sensitive to social conditions.”  Sloan EK, et al. Social stress enhances sympathetic innervation of primate lymph nodes: mechanisms and implications for viral pathogenesis. J Neurosci. 2007; 27(33):8857–8865.

9 Social Factors and Genetics  “Early experience affects every aspect of behavior and biology, including gene expression.”  “The environment can affect genes”  “Forcing some to turn on and others to turn off.”  Cacioppo JT, Hawkley LC, Crawford LE, et al. Loneliness and Health: Potential Mechanisms. Psychosomatic Med. 2002;64(3), 407-417.

10 TOPICS  I. Pregnancy: “Fetal Origins”  A. Birth weight  B. Maternal obesity, diabetes  C. Maternal malnutrition: Starvation  D. Maternal stress, depression  E. Maternal environment: Air pollution  II. Childhood environment and experiences

11 I. PREGNANCY  Known: Mother’s environment impacts fetus.  “Biological postcards from the world outside”  Food, drink, air quality, common chemicals, medications, emotions, activity, toxins, etc.  Continue to affect health into adulthood  Paul, AM. Origins: How the nine months before birth shape the rest of our lives. NY: Simon & Schuster/Free Press, 2010.

12 Prenatal Origins of Adult Disease  Heart Disease Study (Britain, N = 15,000)  Highest rates found in poorest regions  Correlate finding: Small birth size  Hypothesis: Inadequate prenatal nutrition?  Suggested: Heart disease due to prenatal factor  Poor nutrition during gestation  DJP Barker. Developmental origins of adult disease. Euro J Epidem 2003; 18(8):733-736.

13 Birth Weight and Adult Health  Nurses’ Health Study (Boston)  Longitudinal: 1976-1997, N=121,700  Birth weight and mortality  INVERSELY associated for:  Cardiovascular disease  Coronary heart disease  Stroke  Rich-Edwards J. Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976. BMJ 1997;315:396.

14 Nurses Study (continued)  Largely independent of  Adult weight  Hypertension  Diabetes  And NOT related to  Childhood socioeconomic status or  Adult lifestyle

15 Birth Weight and Diabetes  Low birth weight  Increased the risk for DIABETES  As an adult.  Jimenez-Chillaron, JC. β-Cell Secretory Dysfunction in the Pathogenesis of Low Birth Weight–Associated Diabetes. Diabetes, March 2005; 54 (3): 702-711.

16 Pregnancy Weight Gain  Mother’s weight gain during pregnancy  The greater her weight gain,  The higher the risk that  The child would be overweight by age 3.  Kral J, et al. Large maternal weight loss from obesity surgery prevents transmission of obesity to children who were followed for 2 to 18 years. Pediatrics, 118 #6. Dec 1, 2006 pp. e1644 -e1649

17 Obesity (cont.)  Siblings born after the  Mother’s bariatric surgery and  Subsequent weight loss  Had lower birth weights and  Were 52% less likely to become obese  Compared to their older siblings who were born prior to mother’s bariatric surgery  Ibid.

18 Childhood Obesity  Mechanism:  Post-surgery babies processed fats and carbohydrates in a healthier way.  The risk for childhood obesity  May be programmed in the womb  By mother’s pregnancy weight gain.  Ibid.

19 Maternal DIABETES  Known: Significant genetic factor for diabetes  ?: Effect of mother’s high blood sugar on fetus?  Longitudinal study with Pima Indians (AZ)  Conclusion:  “Exposure to maternal diabetes in utero  “Accounts for most of the type 2 diabetes  “Among Pima children over the past 30 years.”  Dabelea, Knowles, Pettitt. Effect of diabetes in pregnancy on offspring: Follow-up research in the Pima Indians. J Mat-Fetal Neonatal Med 2000; 9(1): 83-88.

20 Pregnancy Nutrition  Research with pregnant mice  Fed cruciferous vegetables (broccoli, cabbage)  Decreased cancer risk in offspring  Following exposure to a known carcinogen  Healthy nutrition conferred  “Lifelong chemo-protection”  S1043661807000321

21 Pregnancy Malnutrition  Extreme example: Starvation  Crop failures, food blockades during wars  Offspring had higher risk for schizophrenia  Maternal malnutrition may disrupt neural development of fetus.  Smith, CA. Effect of wartime starvation in Holland upon pregnancy and its product. Am J Obstet Gynecol. 1947;53(4):599-608.  [Also: famine during China’s “Great Leap Forward”]

22 Maternal Stress  Stress hormones may impact intrauterine environment, increasing risk of:  Premature delivery  Low birth weight  May affect fetus’ developing nervous system  Temperament (e.g. “reactivity”)  Increased sensitivity to stress  Increased risk for mental illness

23 “Fetal Origins” Hypothesis  Growing body of evidence  Woman’s distressed mental state during pregnancy may negatively affect fetus.  Psychological state during pregnancy can have effects across the child’s lifespan.  Kinsella MT, Monk C. Impact of maternal stress, depression and anxiety on fetal neurobehavioral development. OB Gyn, Sept 2009, 52 (3): 425-440.

24 Environmental Toxins Example: Air Pollution  Exposure to traffic air pollution during pregnancy (N=500, New York City)  Outcomes: Prematurity, heart malformations  40% of the babies had subtle DNA damage attributed to the pollution  Cognitively delayed at age 3, lower IQ at age 5  F. Perera et al. Effects of transplacental exposure to environmental pollutants. Environ Health Perspectives 2003; 111 (2):201-205.

25 “Fetal Origins” of Illness  Cancer  Hypertension  Cardiovascular  Allergies  Asthma  Diabetes  Obesity  Mental illness  Arthritis  Osteoporosis  Cognitive decline  (Paul 2010)

26 CONVERSELY It’s frequently the Intrauterine environment That makes things go right In later life. (Paul 2010)

27 National Children’s Study  GOAL: Identify the developmental roots of health and disease  N = 10, 000 pregnant women  Longitudinal: Fetus to age 21  Federally funded 2009  First results expected 2012  Causes of premature birth and birth defects 

28 Project VIVA  Effects of childhood experiences on health  Longitudinal: N = 2000+ children in utero  Fetal origins of:  Asthma, Allergies  Obesity, Heart disease  Brain development  Pereira, et al. Predictors of Change in Physical Activity During and After Pregnancy. Prev Med 2007; 32(4):312-19.

29 “The New Genetics”  “Research in social genomics has now clearly established that our interpersonal world  “Exerts biologically significant effect s on the molecular composition of the human body.”  “Social regulation of human gene expression”  Cole, SW. Curr Dir Psychol Sci. 2009 June 1; 18(3): 132–137.  df/nihms-257906.pdf

30 FAMILY PHYSICIANS  Catbird seat: Prevention agenda  Patient education and counseling  Early detection and comprehensive care  Multi-generational impact of focus on healthy lifestyle and preventive care

31 MAIN POINTS  New explanations are emerging for chronic medical problems.  Environmental factors can affect gene expression and determine phenotype.  The social environment can ultimately determine our genetic profile.  Follow the burgeoning research. The End

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