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Genetic admixture, adipocytokines, and adiposity in Black Americans: the Health, Aging, and Body Composition study

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Abstract

Adipocytokines are a subset of cytokines produced by adipose tissue and are associated with risk of type II diabetes and atherosclerosis. Levels of adipocytokines differ between Black and White Americans, even after adjustment for differences in adiposity, diseases associated with adipocytokines including type 2 diabetes and cardiovascular disease, and general socioeconomic status indicators such as income. We used a series of ancestry informative markers to estimate genetic ancestry in a population-based study of older Black Americans, and examined the association between genetic ancestry and adipocytokines and soluble receptors to help determine which of these may be most amenable to admixture mapping. We typed 35 ancestry informative markers in 1,241 self-reported Black Americans with available DNA from the Health, Aging, and Body Composition (Health ABC) study with available DNA and used a maximum likelihood approach to estimate percent European ancestry. We used linear regression models to determine the association between these adipocytokines and percent ancestry, and staged models to examine whether adiposity or other measures affected the associations of genetic ancestry and adipocytokines. Mean European ancestry was 22.3 ± 15.9%. In multivariate adjusted models, the strongest associations observed were between higher European ancestry and interleukin-6 soluble receptor (IL-6 SR), C-reactive protein (CRP), and adiponectin levels, with interleukin-2 soluble receptor (IL-2 SR) and soluble tumor necrosis factor receptor II (TNF-α SR II) also showing more modest but significant associations. The association with adiponectin became stronger after adjustment for adiposity. These novel findings suggest that admixture mapping may identify genetic factors influencing the levels of IL-6 SR, CRP, IL-2 SR, and adiponectin.

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References

  • Agirbalsi M (2005) Pivotal role of plasminogen-activator inhibitor 1 in vascular disease. Int J Clin Pract 59(1):102–106

    Article  Google Scholar 

  • Araneta MG, Barrett-Connor E (2005) Ethnic differences in visceral adipose tissue and type 2 diabetes: Filipino, African-American and white women. Obes Res 13:1458–1465

    PubMed  Google Scholar 

  • Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265

    Article  PubMed  CAS  Google Scholar 

  • Cesari M, Penninx BW, Newman AB, Kritchevsky SB, Nicklas BJ, Sutton-Tyrrell K, Rubin SM, Ding J, Simonsick EM, Harris TB, Pahor M (2003) Inflammatory markers and onset of cardiovascular events. Circulation 108(19):2317–2322

    Article  PubMed  CAS  Google Scholar 

  • Chakraborty R, Ferrell RE, Stern MP, Haffner SM, Hazuda HP, et al (1986) Relationship of prevalence of non-insulin-dependent diabetes mellitus to Amerindian admixture in the Mexican Americans of San Antonio, Texas. Genet Epidemiol 3:435–454

    Article  PubMed  CAS  Google Scholar 

  • Choudhry S, Coyle NE, Tang H, Salari K, Lind D, et al (2006) Population stratification confounds genetic association studies among Latinos. Hum Genet 118(5):652–664

    Article  PubMed  Google Scholar 

  • Cushman M, Arnold AM, Psaty BM, Manolio TA, Kuller LH, Burke GL, Polak JF, Tracy RP (2005) C-reactive protein and the 10-year incidence of coronary heart disease in older men and women. Circulation 112:25–31

    Article  PubMed  CAS  Google Scholar 

  • Festa A, D’Agostino R Jr, Tracy RP, Haffner SM (2002) Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51:1131–1137

    Article  PubMed  CAS  Google Scholar 

  • Festa A, D’Agostino R, Rich SS, Jenny NS, Tracy RP, et al (2003) Promotor (4G/5G) plasminogen activator inhibitor-1 genotype and plasminogen activator inhibitor-1 levels in blacks, Hispanics, and non-Hispanic whites. Circulation 107:2422–2427

    Article  PubMed  CAS  Google Scholar 

  • Freedman ML, Haiman CA, Patterson N, McDonald GJ, Tandon A, et al (2006) Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc Natl Acad Sci USA 103(38):14068–14073

    Article  PubMed  CAS  Google Scholar 

  • Haffner SM, Mykkanen L, Rainwater DL, Karhapaa P, Laakso M (1999) Is leptin concentration associated with the insulin resistance syndrome in nondiabetic men? Obes Res 7:164–169

    PubMed  CAS  Google Scholar 

  • Hoggart CJ, Shriver MD, Kittles RA, Clayton DG, McKeigue PM (2004) Design and analysis of admixture mapping studies. Am J Hum Genet 74:965–978

    Article  PubMed  CAS  Google Scholar 

  • Hsueh W-C, Kanaya A, Reich DE, Wu SH, McDonald GJ, et al (2006) Association among genetic admixture, visceral fat and type 2 diabetes in the health ABC study. Diabetes 55(Suppl 1):A259

    Google Scholar 

  • Hulver MW, Saleh O, MacDonald KG, Pories WJ, Barakat HA (2004) Ethnic differences in adiponectin levels. Metabolism 53(1):1–3

    Article  PubMed  CAS  Google Scholar 

  • Kanaya AM, Wassel Fyr CL, Goodpaster B, Harris TB, Tylavsky F, Cummings SR (2006a) Adipocytokines and incident diabetes in older adults: the independent effect of PAI-1. Arch Int Med 166:350–356

    Article  CAS  Google Scholar 

  • Kanaya AM, Wassel Fyr C, Cesari M, Harris T, et al (2006b) Elevated total adiponectin concentration is associated with increased risk of coronary heart disease in older black adults but not in whites. J Clin Endocrinol Metab 91(12):5044–5050

    Article  CAS  Google Scholar 

  • Khera A, McGuire DK, Murphy SA, Stanek HG, Das SR, et al (2005) Race and gender differences in C-reactive protein. J Am Coll Cardiol 46:464–469

    Article  PubMed  CAS  Google Scholar 

  • Kohler HP, Grant PJ (2000) Plasminogen-activator inhibitor type 1 and coronary artery disease. NEJM 342(24):1792–1801

    Article  PubMed  CAS  Google Scholar 

  • McKeigue PM, Carpenter JR, Parra EJ, Shriver MD (2000) Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African-American populations. Ann Hum Genet 64:171–186

    Article  PubMed  CAS  Google Scholar 

  • McKeigue PM (2005) Prospects for admixture mapping of complex traits. Am J Hum Genet 76:1–7

    Article  PubMed  CAS  Google Scholar 

  • Parra EJ, Marcini A, Akey J, Martinson J, Batzer MA, et al (1998) Estimating African American admixture proportions by use of population-specific alleles. Am J Hum Genet 63:1839–1851

    Article  PubMed  CAS  Google Scholar 

  • Patterson N, Hattangadi N, Lane B, Lohmueller KE, Hafler DA, et al (2004) Methods for high-density admixture mapping of disease genes. Am J Hum Genet 74:979–1000

    Article  PubMed  CAS  Google Scholar 

  • Pickup JC, Chusney GD, Thomas SM, Burt D (2000) Plasma interleukin-6, tumour necrosis factor alpha and blood cytokine production in type 2 diabetes. Life Sci 67:291–300

    Article  PubMed  CAS  Google Scholar 

  • Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, et al (2004) Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 291(14):1730–1737

    Article  PubMed  CAS  Google Scholar 

  • Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM (2001) C-reactive protein, interleukin 6 and risk of developing type 2 diabetes mellitus. JAMA 286:327–334

    Article  PubMed  CAS  Google Scholar 

  • Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959

    PubMed  CAS  Google Scholar 

  • Reich D, Patterson N, De Jager PL, McDonald GJ, Waliszewska A, et al (2005) A whole genome admixture scan finds a candidate locus for multiple sclerosis susceptibility. Nat Genet 37(10):1113–1118

    Article  PubMed  CAS  Google Scholar 

  • Reiner AP, Ziv E, Lind DL, Nieverelt CM, Schork NJ, et al (2005) Population structure, admixture, and aging-related phenotypes in African American adults: the cardiovascular health study. Am J Hum Genet 76:463–477

    Article  PubMed  CAS  Google Scholar 

  • Risch N, Burchard E, Ziv E, Tang H (2002) Categorization of humans in biomedical research: genes, race and disease. Genome Biol 3(7):1–12

    Article  Google Scholar 

  • Rosenberg NA, Li LM, Ward R, Pritchard JK (2003) Informativeness of genetic markers for inference of ancestry. Am J Hum Genet 73:1402–1422

    Article  PubMed  CAS  Google Scholar 

  • Ruhl CE, Everhart JE (2002) Leptin concentrations in the United States: relations with demographic and anthropometric measures. Am J Clin Nutr 74:295–301

    Google Scholar 

  • Ruhl CE, Everhart JE, Ding J, Goodpaster BH, Kanaya AM, Simonsick EM, Tylavsky FA, Harris TB (2004) Serum leptin concentrations and body adipose measures in older black and white adults. Am J Clin Nutr 80:576–583

    PubMed  CAS  Google Scholar 

  • Ryan AS, Nicklas BJ, Berman DM (2002) Racial differences in insulin resistance and mid-thigh fat deposition in postmenopausal women. Obes Res 10:336–344

    Article  PubMed  Google Scholar 

  • Shriver MD, Smith MW, Jin L, Marcini A, Akey JM, et al (1997) Ethnic-affiliation estimation by the use of population-specific DNA markers. Am J Hum Genet 60:957–964

    PubMed  CAS  Google Scholar 

  • Shriver MD, Parra EJ, Dios S, Bonilla C, Norton H, et al (2003) Skin pigmentation, biogeographical ancestry and admixture mapping. Hum Genet 112(4):387–399

    PubMed  Google Scholar 

  • Smith MW, Patterson N, Lautenberger JA, Truelove AL, McDonald GJ, et al (2004) A high density admixture map for disease gene discovery in African Americans. Am J Hum Genet 74:1001–1013

    Article  PubMed  CAS  Google Scholar 

  • Steinburg GR, Michell BJ, van Denderen BJ, Watt MJ, Carey AL, et al (2006) Tumor necrosis factor-alpha induced skeletal muscle insulin resistance involves suppression of AMP-kinase signaling. Cell Metab 4(6):465–474

    Article  CAS  Google Scholar 

  • Tang H, Jorgenson E, Gadde M, Kardia SLR, Rao DC, et al (2006) Racial admixture and its impact on BMI and blood pressure in African and Mexican Americans. Hum Genet 119:624–633

    Article  PubMed  Google Scholar 

  • Tuomisto K, Jousilahti P, Sundvall J, Pajunen P, Salomaa V (2006) C-reactive protein, interleukin-6 and tumor necrosis factor alpha as predictors of incident coronary and cardiovascular events and total mortality. Thromb Haemost 95:511–518

    PubMed  CAS  Google Scholar 

  • Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, et al (2002) Relationship of interleukin-6 and tumor necrosis factor-α with muscle mass and muscle strength in elderly men and women: the health ABC study. J Gerontol 57A(5):M326–M332

    CAS  Google Scholar 

  • Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935

    Article  PubMed  CAS  Google Scholar 

  • Winkler G, Salamon F, Salamon D, Speer G, Simon K, Cseh K (1998) Elevated serum tumour necrosis factor-alpha levels can contribute to the insulin resistance in type II (non-insulin-dependent) diabetes and in obesity. Diabetologia 41:860–861

    Article  PubMed  CAS  Google Scholar 

  • Wittke-Thompson JK, Plushnikov A, Cox NJ (2005) Rational inferences about departures from hardy-weinberg equilibrium. Am J Hum Genet 76:967–986

    Article  PubMed  CAS  Google Scholar 

  • Yuan G, Zhou L, Tang J, Yang Y, Gu W, Li F, Hong J, Gu Y, Li X, Ning G, Chen M (2006) Serum CRP levels are equally elevated in newly diagnosed type 2 diabetes and impaired glucose tolerance and related to adiponectin levels and insulin sensitivity. Diabetes Res Clin Pract 72(3):244–250

    Article  PubMed  CAS  Google Scholar 

  • Zhu X, Luke A, Cooper RS, Quertermous T, Hanis C, et al (2005) Admixture mapping for hypertension loci with genome-scan markers. Nat Genet 37(2):118–119

    Article  CAS  Google Scholar 

Download references

Acknowledgments

CWF is supported by the NIH training grant in cardiovascular genetic epidemiology (T32 HL097972). EZ is supported by a career transition award from the NCI (K22CA109351). The Health ABC study was funded by NIA contract numbers (N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106). This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Role of the sponsor: this study was funded via contracts with the National Institute on Aging and included substantial involvement of NIA staff in data collection, analysis, and interpretation of these results.

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Authors and Affiliations

  1. Department of Epidemiology, University of Minnesota, Minneapolis, 1300 South 2nd Street, Suite 300, Minneapolis, MN, 55454-1015, USA

    Christina L. Wassel Fyr

  2. University of California, San Francisco, CA, USA

    Alka M. Kanaya, Wen-Chi Hsueh & Elad Ziv

  3. California Pacific Medical Center, San Francisco, CA, USA

    Steve R. Cummings

  4. Harvard University, Boston, MA, USA

    David Reich

  5. University of Washington, Seattle, WA, USA

    Alexander P. Reiner

  6. National Institutes of Health, Bethesda, MD, USA

    Tamara B. Harris

  7. University of Pittsburgh, Pittsburgh, PA, USA

    Susan Moffett & Iva Miljkovic-Gacic

  8. University of Tennessee, Memphis, TN, USA

    Rongling Li

  9. Wake Forest University, Winston-Salem, NC, USA

    Jingzhong Ding

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  1. Christina L. Wassel Fyr
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for the Health, Aging, Body Composition Study

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Correspondence to Christina L. Wassel Fyr.

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Wassel Fyr, C.L., Kanaya, A.M., Cummings, S.R. et al. Genetic admixture, adipocytokines, and adiposity in Black Americans: the Health, Aging, and Body Composition study. Hum Genet 121, 615–624 (2007). https://doi.org/10.1007/s00439-007-0353-z

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