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Genetic analysis of adiponectin and obesity in Hispanic families: the IRAS Family Study

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Abstract

Adiponectin, coded for by the APM1 gene, is a novel adipocyte-derived hormone implicated in energy homeostasis and obesity. Several genetic studies have observed evidence of association between APM1 gene polymorphisms and features of the metabolic syndrome, such as insulin resistance and obesity. As part of a comprehensive genetic analysis of the APM1 gene, we have screened 96 unrelated individuals for polymorphisms in the promoter, coding regions, and 3’untranslated region (UTR). Three promoter single-nucleotide polymorphisms (SNPs), two rare coding SNPs (G113A and T1233C), and 13 SNPs in the 3’UTR were identified. Eighteen SNPs were genotyped in 811 Hispanic individuals from 45 families in the IRAS Family Study (IRASFS). SNPs were tested for association with six obesity quantitative traits (body mass index, waist, waist:hip ratio, subcutaneous adipose tissue, visceral adipose tissue, and visceral:subcutaneous ratio). Significant evidence of association to at least one of the obesity traits was identified in seven of the 18 SNPs (<0.001–0.05). The promoter SNP INS CA-11156 was the most consistently associated SNP and was associated significantly with all measures of obesity, except the visceral:subcutaneous ratio (P-values 0.009–0.03). Haplotype analysis supported this evidence of association, with haplotypes containing an insertion of one CA repeat at position −11156 consistently being associated with lower obesity values (P-value <0.001–0.05). The adiponectin polymorphisms, in particular those in the promoter region, thus show significant association with obesity measures in the Hispanic population. Additional studies are needed to confirm our findings and determine which polymorphism causes the functional effect.

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References

  • Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79–83

    Google Scholar 

  • Bacci S, Menzaghi C, Ercolino T, Ma X, Rauseo A, Salvemini L, Vigna C, Fanelli R, Di Mario U, Doria A, Trischitta V (2004) The +276 G/T single nucleotide polymorphism of the adiponectin gene is associated with coronary artery disease in type 2 diabetic patients. Diabetes Care 27:2015–2020

    Google Scholar 

  • Buetow KH, Edmonson M, MacDonald R, Clifford R, Yip P, Kelley J, Little DP, Strausberg R, Koester H, Cantor CR, Braun A (2001) High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Proc Natl Acad Sci USA 98:581–584

    Google Scholar 

  • Dudbridge F (2003) Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 25:115–121

    Google Scholar 

  • Duncan BB, Schmidt MI, Pankow JS, Bang H, Couper D, Ballantyne CM, Hoogeveen RC, Heiss G (2004) Adiponectin and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes 53:2473–2478

    Google Scholar 

  • Fenech AG, Billington CK, Swan C, Richards S, Hunter T, Ebejer MJ, Felice AE, Ellul-Micallef R, Hall IP (2004) Novel polymorphisms influencing transcription of the human CHRM2 gene in airway smooth muscle. Am J Respir Cell Mol Biol 30:678–686

    Google Scholar 

  • Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 98:2005–2010

    Google Scholar 

  • Fumeron F, Aubert R, Siddiq A, Betoulle D, Pean F, Hadjadj S, Tichet J, Wilpart E, Chesnier MC, Balkau B, Froguel P, Marre M (2004) Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study. Diabetes 53:1150–1157

    Google Scholar 

  • Funke-Kaiser H, Thomas A, Bremer J, Kovacevic SD, Scheuch K, Bolbrinker J, Theis S, Lemmer J, Zimmermann A, Zollmann FS, Herrmann SM, Paul M, Orzechowski HD (2003) Regulation of the major isoform of human endothelin-converting enzyme-1 by a strong housekeeping promoter modulated by polymorphic microsatellites. J Hypertens 21:2111–2124

    Google Scholar 

  • Gu HF, Abulaiti A, Ostenson CG, Humphreys K, Wahlestedt C, Brookes AJ, Efendic S (2004) Single nucleotide polymorphisms in the proximal promoter region of the adiponectin (APM1) gene are associated with type 2 diabetes in Swedish caucasians. Diabetes 53 (Suppl 1):S31–S35

    Google Scholar 

  • Guo X, Saad MF, Langefeld CD, Beck S, Taylor K, Jinagouda S, Bergman RN, Sutton BS, Bowden DW, Rotter J (2004) Genomewide linkage of plasma adiponectin reveals a major locus on chromosome 3q; the IRAS Family Study. Diabetes 53 (Supp 2):A273

    Google Scholar 

  • Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K, Yamauchi T, Otabe S, Okada T, Eto K, Kadowaki H, Hagura R, Akanuma Y, Yazaki Y, Nagai R, Taniyama M, Matsubara K, Yoda M, Nakano Y, Tomita M, Kimura S, Ito C, Froguel P, Kadowaki T (2002) Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 51:536–540

    Google Scholar 

  • Henkin L, Bergman RN, Bowden DW, Ellsworth DL, Haffner SM, Langefeld CD, Mitchell BD, Norris JM, Rewers M, Saad MF, Stamm E, Wagenknecht LE, Rich SS (2003) Genetic epidemiology of insulin resistance and visceral adiposity. The IRAS Family Study design and methods. Ann Epidemiol 13:211–217

    Google Scholar 

  • Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599

    Google Scholar 

  • Hu E, Liang P, Spiegelman BM (1996) AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 271:10697–10703

    Google Scholar 

  • Hu FB, Doria A, Li T, Meigs JB, Liu S, Memisoglu A, Hunter D, Manson JE (2004) Genetic variation at the adiponectin locus and risk of type 2 diabetes in women. Diabetes 53:209–213

    Google Scholar 

  • Kissebah AH, Sonnenberg GE, Myklebust J, Goldstein M, Broman K, James RG, Marks JA, Krakower GR, Jacob HJ, Weber J, Martin L, Blangero J, Comuzzie AG (2000) Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci USA 97:14478–14483

    Google Scholar 

  • Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y (2002) Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 8:731–737

    Google Scholar 

  • Menzaghi C, Ercolino T, Di Paola R, Berg AH, Warram JH, Scherer PE, Trischitta V, Doria A (2002) A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 51:2306–2312

    Google Scholar 

  • Mori Y, Otabe S, Dina C, Yasuda K, Populaire C, Lecoeur C, Vatin V, Durand E, Hara K, Okada T, Tobe K, Boutin P, Kadowaki T, Froguel P (2002) Genome-wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate Loci on 7p and 11p. Diabetes 51:1247–1255

    Google Scholar 

  • Neter J, Wasserman W, Kutner MH (1990) Applied linear statistical models: regression, analysis of variance, and experimental designs, 3rd edn. Homewood, Irwin

    Google Scholar 

  • O’Connell JR (2000) Zero-recombinant haplotyping: applications to fine mapping using SNPs. Genet Epidemiol 19 (Suppl 1):S64–S70

    Google Scholar 

  • O’Connell JR, Weeks DE (1998) PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 63:259–266

    Google Scholar 

  • Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (1999) Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100:2473–2476

    Google Scholar 

  • Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (2000) Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 102:1296–1301

    Google Scholar 

  • Populaire C, Mori Y, Dina C, Vasseur F, Vaxillaire M, Kadowaki T, Froguel P (2003) Does the −11377 promoter variant of APM1 gene contribute to the genetic risk for type 2 diabetes mellitus in Japanese families? Diabetologia 46:443–445

    Google Scholar 

  • Rich SS, Bowden DW, Haffner SM, Norris JM, Saad MF, Mitchell BD, Rotter JI, Langefeld CD, Wagenknecht LE, Bergman RN (2004) Identification of quantitative trait loci for glucose homeostasis: the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. Diabetes 53:1866–1875

    Google Scholar 

  • Shapiro L, Scherer PE (1998) The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol 8:335–338

    Google Scholar 

  • Shimajiri S, Arima N, Tanimoto A, Murata Y, Hamada T, Wang KY, Sasaguri Y (1999) Shortened microsatellite d(CA)21 sequence down-regulates promoter activity of matrix metalloproteinase 9 gene. FEBS Lett 455:70–74

    Google Scholar 

  • Stumvoll M, Tschritter O, Fritsche A, Staiger H, Renn W, Weisser M, Machicao F, Haring H (2002) Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes 51:37–41

    Google Scholar 

  • Takahashi M, Arita Y, Yamagata K, Matsukawa Y, Okutomi K, Horie M, Shimomura I, Hotta K, Kuriyama H, Kihara S, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (2000) Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord 24:861–868

    Google Scholar 

  • Tschritter O, Fritsche A, Thamer C, Haap M, Shirkavand F, Rahe S, Staiger H, Maerker E, Haring H, Stumvoll M (2003) Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism. Diabetes 52:239–243

    Google Scholar 

  • Vasseur F, Helbecque N, Dina C, Lobbens S, Delannoy V, Gaget S, Boutin P, Vaxillaire M, Lepretre F, Dupont S, Hara K, Clement K, Bihain B, Kadowaki T, Froguel P (2002) Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet 11:2607–2614

    Google Scholar 

  • Vionnet N, Hani El H, Dupont S, Gallina S, Francke S, Dotte S, De Matos F, Durand E, Lepretre F, Lecoeur C, Gallina P, Zekiri L, Dina C, Froguel P (2000) Genomewide search for type 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21–q24. Am J Hum Genet 67:1470–1480

    Google Scholar 

  • Zeger SL, Liang KY (1986) Longitudinal data analysis for discrete and continuous outcomes. Biometrics 42:121–130

    Google Scholar 

  • Zhu X, Cooper RS, Luke A, Chen G, Wu X, Kan D, Chakravarti A, Weder A (2002) A genome-wide scan for obesity in African-Americans. Diabetes 51:541–544

    Google Scholar 

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Acknowledgements

This work was supported by NIH Grants R01 HL60894, HL61210, HL61019, HL60894, and HL60931.

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Authors and Affiliations

  1. Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA

    Beth S. Sutton, Stefanie Weinert & Donald W. Bowden

  2. Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA

    Donald W. Bowden

  3. Centers for Human Genomics, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA

    Beth S. Sutton, Stefanie Weinert & Donald W. Bowden

  4. Department of Public Health Sciences, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA

    Carl D. Langefeld, Adrienne H. Williams & Joel K. Campbell

  5. Department of Medicine, University of California at Los Angeles, Los Angeles, Calif., USA

    Mohammed F. Saad

  6. Department of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, Tex., USA

    Steven M. Haffner

  7. Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colo., USA

    Jill M. Norris

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  1. Beth S. Sutton
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  9. Donald W. Bowden
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Correspondence to Donald W. Bowden.

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Sutton, B.S., Weinert, S., Langefeld, C.D. et al. Genetic analysis of adiponectin and obesity in Hispanic families: the IRAS Family Study. Hum Genet 117, 107–118 (2005). https://doi.org/10.1007/s00439-005-1260-9

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