C-reactive protein and telomerase reverse transcriptase (TERT) associate with chronic disease markers in a sample from low-income neighborhoods in Detroit, Michigan

Abstract

Racial and ethnic minorities in economically deprived inner cities experience high rates of chronic diseases compared to neighborhoods with higher socioeconomic status (SES). However, these economically deprived populations are understudied in terms of biomarkers associated with chronic disease risk which include C-reactive protein (CRP), telomerase reverse transcriptase (TERT), and glycosylated hemoglobin (A1C). We examined relationships between CRP and TERT and chronic disease indicators (body mass index [BMI] and A1C) in two low-income, predominantly African American (AA) neighborhoods in Detroit, Michigan. Sixty-nine adults (43 females, 26 males, mean age 46 years [y], standard deviation [SD] ​= ​15.9) completed a health survey, anthropometry, and finger stick blood tests. A1C was measured using A1CNow test strips, and CRP and TERT levels were measured using enzyme-linked immunosorbent assay (ELISA) with samples extracted from dried blood spots. We examined CRP (mean ​= ​4.9, SD ​= ​3.1), TERT (mean ​= ​32.5, SD ​= ​15.1), and A1C (mean ​= ​5.4, SD ​= ​1.0) by BMI category. We fitted restricted maximum likelihood regression models to evaluate associations between CRP, TERT, BMI, and A1C, after adjustment for demographics and inclusion of a random effect for the neighborhood. In this predominantly AA sample (91%, 63/69), 68% had levels of CRP (means ​= ​4.8 ​mg/L, SD ​= ​3.0 for AAs; 6.4 ​mg/L, SD ​= ​3.9 for all others) indicative of chronic inflammation (CRP greater than 3 ​mg/L). BMI was significantly associated with CRP (p ​= ​0.004) and TERT (p ​= ​0.026). TERT levels indicate that being overweight is associated with markers of chromosome remodeling, suggestive of chronic disease. CRP followed a similar trend with overweight individuals having higher inflammation and risk of chronic disease. Our findings warrant further exploration of additional factors that may influence CRP and TERT. Furthermore, examining populations in a more ethnically and/or economically diverse, yet still high proportion minority, sample will fill a knowledge gap in this understudied field.

Keywords

Ethnic minority / Inequality / Chronic disease / Urban / Biomarkers

References

[[1]] CW Kuzawa, E Sweet. Epigenetics and the embodiment of race: developmental origins of US racial disparities in cardiovascular health. Am J Hum Biol, 21 (1) ( 2009), pp. 2-15, DOI: 10.1002/ajhb.20822

[[2]] C Dye. Health and urban living. Science, 319 (5864) ( 2008), pp. 766-769, DOI: 10.1126/science.1150198

[[3]] TV Johnson, A Abbasi, VA Master. Systematic review of the evidence of a relationship between chronic psychosocial stress and C-reactive protein. Mol Diagn Ther, 17 (3) ( 2013), pp. 147-164, DOI: 10.1007/s40291-013-0026-7

[[4]] A Nazmi, CG Victora.Socioeconomic and racial/ethnic differentials of C-reactive protein levels: a systematic review of population-based studies. BMC Publ Health, 7 ( 2007), p. 212, DOI: 10.1186/1471-2458-7-212

[[5]] A Kelley-Hedgepeth, DM Lloyd-Jones, A Colvin, et al.. Ethnic differences in C-reactive protein concentrations. Clin Chem, 54 (6) ( 2008), pp. 1027-1037, DOI: 10.1373/clinchem.2007.098996

[[6]] RH Straub, M Cutolo. Psychoneuroimmunology-developments in stress research. Wien Med Wochenschr, 168 (3-4) ( 2018), pp. 76-84, DOI: 10.1007/s10354-017-0574-2

[[7]] BB Duncan, G Heiss. Nonenzymatic Glycosylation of proteins-A new tool for assessment of cumulative hyperglycemia in epidemiologic studies, past and future. Am J Epidemiol, 120 (2) ( 1984), pp. 169-189, DOI: 10.1093/oxfordjournals.aje.a113880

[[8]] S Šimić, T Svaguša, I Prkačin, T Bulum. Relationship between hemoglobin A1c and serum troponin in patients with diabetes and cardiovascular events. J Diabetes Metab Disord, 18 (2) ( 2019), pp. 693-704, DOI: 10.1007/s40200-019-00460-9

[[9]] Y Liu, YM Yang, J Zhu, HQ Tan, Y Liang, JD Li.Prognostic significance of hemoglobin A1c level in patients hospitalized with coronary artery disease. A systematic review and meta-analysis. Cardiovasc Diabetol, 10 ( 2011), p. 98, DOI: 10.1186/1475-2840-10-98

[[10]] FA Fonseca, MC Izar. High-Sensitivity C-reactive protein and cardiovascular disease across countries and ethnicities. Clinics, 71 (4) ( 2016), pp. 235-242, DOI: 10.6061/clinics/ 2016(04)11

[[11]] S Verma, ET Yeh. C-reactive protein and atherothrombosis—beyond a biomarker: an actual partaker of lesion formation. Am J Physiol Regul Integr Comp Physiol, 285 (5) ( 2003), pp. R1253-R1256, DOI: 10.1152/ajpregu.00170.2003

[[12]] TA Pearson, GA Mensah, RW Alexander, et al.. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation, 107 (3) ( 2003), pp. 499-511, DOI: 10.1161/01.cir.0000052939.59093.45

[[13]] AH Berg, PE Scherer. Adipose tissue, inflammation, and cardiovascular disease. Circ Res, 96 (9) ( 2005), pp. 939-949, DOI: 10.1161/01.RES.0000163635.62927.34

[[14]] K de Punder, C Heim, PD Wadhwa, S Entringer. Stress and immunosenescence: the role of telomerase. Psychoneuroendocrinology, 101 ( 2019), pp. 87-100, DOI: 10.1016/j.psyneuen.2018.10.019

[[15]] M Porika, R Tippani, A Mohammad, SR Bollam, SD Panuganti, S Abbagani. Evaluation of serum human telomerase reverse transcriptase as a novel marker for cervical cancer. Int J Biol Markers, 26 (1) ( 2011), pp. 22-26, DOI: 10.5301/JBM.2011.6352

[[16]] SC Akincilar, B Unal, V Tergaonkar. Reactivation of telomerase in cancer. Cell Mol Life Sci, 73 (8) ( 2016), pp. 1659-1670, DOI: 10.1007/s00018-016-2146-9

[[17]] R Leão, JD Apolónio, D Lee, et al.. Mechanisms of human telomerase reverse transcriptase (h TERT) regulation: clinical impacts in cancer. J Biomed Sci, 25 (1) ( 2018), p. 22, DOI: 10.1186/s12929-018-0422-8

[[18]] TW McDade. Cambridge University Press (Measuring immune function: markers of cell-mediated immunity and inflammation in dried blood spots. G.H. Ice, G.D. James (Eds.), A Practical Guide to Measuring Stress in the Field, 2007), pp. 181-208

[[19]] N Grüner, O Stambouli, RS Ross. Dried blood spots-preparing and processing for use in immunoassays and in molecular techniques. JoVE, 97 ( 2015), Article 52619, DOI: 10.3791/52619

[[20]] PA Demirev. Dried blood spots: analysis and applications. Anal Chem, 85 (2) ( 2013), pp. 779-789, DOI: 10.1021/ac303205m

[[21]] K Kearns, A Dee, AP Fitzgerald, E Doherty, I Perry.Chronic disease burden associated with overweight and obesity in Ireland: the effects of a small BMI reduction at population level. BMC Publ Health, 14 ( 2014), p. 143, DOI: 10.1186/1471-2458-14-143

[[22]] A Chandra, et al..IJ Neeland, JD Berry, The relationship of body mass and fat distribution with incident hypertension: observations from the Dallas Heart Study. J Am Coll Cardiol, 64 (10) ( 2014), pp. 997-1002, DOI: 10.1016/j.jacc.2014.05.057

[[23]] AL Pearson, KA Pfeiffer, J Gardiner, et al.. Study of active neighborhoods in Detroit (StAND): study protocol for a natural experiment evaluating the health benefits of ecological restoration of parks. BMC Publ Health, 20 (1) ( 2020), p. 638, DOI: 10.1186/s12889-020-08716-3

[[24]] International Diabetes Federation Guideline Development Group.Global guideline for type 2 diabetes. Diabetes Res Clin Pract, 104 (1) ( 2014), pp. 1-52, DOI: 10.1016/j.diabres.2012.10.001

[[25]] J Ludwig, L Sanbonmatsu, L Gennetian, et al.. Neighborhoods, obesity, and diabetes--a randomized social experiment. N Engl J Med, 365 (16) ( 2011), pp. 1509-1519, DOI: 10.1056/NEJMsa1103216

[[26]] C Szablowski, E Suscha, K Davis, et al.. Point-of-Care HbA1c—a case for diabetes screening and diagnosis. Diabetes, 67 (Supplement 1) ( 2018), p. 1518, DOI: 10.2337/db18-1518-

[[27]] E Brindle, M Fujita, J Shofer, et al.. Serum, plasma, and dried blood spot high-sensitivity C-reactive protein enzyme immunoassay for population research. J Immunol Methods, 362 (1-2) ( 2010), pp. 112-120, DOI: 10.1016/j.jim.2010.09.014

[[28]] JV Mei, JR Alexander, BW Adam, WH Hannon. Use of filter paper for the collection of analysis of human whole blood specimens. J Nutr, 131 (5) ( 2001), pp. 1631S-1636S, DOI: 10.1093/jn/131.5.1631S

[[29]] MF Dallman. Stress-induced obesity and the emotional nervous system. Trends Endocrinol Metab, 21 (3) ( 2010), pp. 159-165, DOI: 10.1016/j.tem.2009.10.004

[[30]] C Stefanaki, P Pervanidou, D Boschiero, GP Chrousos. Chronic stress and body composition disorders: implications for health and disease. Hormones (Basel), 17 (1) ( 2018), pp. 33-43, DOI: 10.1007/s42000-018-0023-7

[[31]] DA Chirinos, LM Garcini, A Seiler, et al.. Psychological and biological pathways linking perceived neighborhood characteristics and body mass index. Ann Behav Med, 53 (9) ( 2019), pp. 827-838, DOI: 10.1093/abm/kay092

[[32]] CA Vella, MA Allison, M Cushman, et al.. Physical activity and adiposity-related inflammation: the MESA. Med Sci Sports Exerc, 49 (5) ( 2017), pp. 915-921, DOI: 10.1249/mss.0000000000001179

[[33]] VA Johnson, A Abbasi, VA Master. Systematic review of the evidence of a relationship between chronic psychosocial stress and C-reactive protein. Mol Diagn Ther, 17 (3) ( 2013), pp. 147-164, DOI: 10.1007/s40291-013-0026-7

[[34]] JB Dowd, T Palermo, L Chyu, E Adam, TW McDade. Race/ethnic and socioeconomic differences in stress and immune function in the National Longitudinal Study of Adolescent Health. Soc Sci Med, 115 ( 2014), pp. 49-55, DOI: 10.1016/j.socscimed.2014.06.011

[[35]] AE Borders, WA Grobman, LB Amsden, TW McDade, LK Sharp, JL Holl.The relationship between self-report and biomarkers of stress in low-income reproductive-age women. Am J Obstet Gynecol, 203 (6) ( 2010), pp. e1-577-e5778, DOI: 10.1016/j. ajog.2010.08.002

The authors wish to thank the study participants and staff, without whom this study would not be possible. We thank Nicole Conner and Rev. Dr. Ventra Asana for their leadership on the study team. We thank Grace Episcopal Church and Lincoln Library for the use of their facilities and their support of this study. We also thank Ben Dougherty and Kim Clevenger for assistance with the field team.