Molecular Biology Reports

, Volume 40, Issue 2, pp 1819–1826 | Cite as

Amerindians show association to obesity with adiponectin gene SNP45 and SNP276: population genetics of a food intake control and “thrifty” gene

  • Antonio Arnaiz-VillenaEmail author
  • Mercedes Fernández-Honrado
  • Diego Rey
  • Mercedes Enríquez-de-Salamanca
  • Sedeka Abd-El-Fatah-Khalil
  • Ignacio Arribas
  • Carmen Coca
  • Manuel Algora
  • Cristina Areces


Adiponectin gene polymorphisms SNP45 and SNP276 have been related to metabolic syndrome (MS) and related pathologies, including obesity. However results of associations are contradictory depending on which population is studied. In the present study, these adiponectin SNPs are for the first time studied in Amerindians. Allele frequencies are obtained and comparison with obesity and other MS related parameters are performed. Amerindians were also defined by characteristic HLA genes. Our main results are: (1) SNP276 T is associated to low diastolic blood pressure in Amerindians, (2) SNP45 G allele is correlated with obesity in female but not in male Amerindians, (3) SNP45/SNP276 T/G haplotype in total obese/non-obese subjects tends to show a linkage with non-obese Amerindians, (4) SNP45/SNP276 T/T haplotype is linked to obese Amerindian males. Also, a world population study is carried out finding that SNP45 T and SNP276 T alleles are the most frequent in African Blacks and are found significantly in lower frequencies in Europeans and Asians. This together with the fact that there is a linkage of this haplotype to obese Amerindian males suggest that evolutionary forces related to famine (or population density in relation with available food) may have shaped world population adiponectin polymorphism frequencies.


Acrp30 ADIPOQ Adiponectin SNP45 Adiponectin SNP276 Amerindians APM1 Diabetes HLA Hypertension Metabolic syndrome Obesity Population genetics rs1501299 rs2241766 Thrifty genes 



This study was supported in part by grants from the Spanish Ministry of Health (FISS PI-11-807) and a Mutua Madrileña Automovilista grants. We thank Javier Alonso Rubio for revision of calculations and paper wording and construction.


  1. 1.
    Nakano Y, Tobe T, Choi-Miura NH, Mazda T, Tomita M (1996) Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem 120:803–812PubMedCrossRefGoogle Scholar
  2. 2.
    Viengchareun S, Zennaro MC, Pascual-Le Tallec L, Lombes M (2002) Brown adipocytes are novel sites of expression and regulation of adiponectin and resistin. FEBS Lett 532:345–350PubMedCrossRefGoogle Scholar
  3. 3.
    Berg AH, Combs TP, Scherer PE (2002) ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 13:84–89PubMedCrossRefGoogle Scholar
  4. 4.
    Mantzoros CS, Li T, Manson JE, Meigs JB, Hu FB (2005) Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in women with type 2 diabetes. J Clin Endocrinol Metab 90:4542–4548PubMedCrossRefGoogle Scholar
  5. 5.
    Kubota N, Yano W, Kubota T, Yamauchi T, Itoh S, Kumagai H et al (2007) Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. Cell Metab 6:55–68PubMedCrossRefGoogle Scholar
  6. 6.
    Alberti KG, Zimmet P, Shaw J (2005) The metabolic syndrome—a new worldwide definition. Lancet 366:1059–1062PubMedCrossRefGoogle Scholar
  7. 7.
    Arnaiz-Villena A, Fernandez-Honrado M, Areces C, Arribas I, Coca C, Enriquez-de-Salamanca M et al (2012) Amerindians normalized waist circumference and obesity diagnosis standardized by biochemical and HLA data. Mol Biol Rep 39:4875–4878PubMedCrossRefGoogle Scholar
  8. 8.
    Rey D, Fernandez-Honrado M, Areces C, Algora M, Abd-El-Fatah-Khalil S, Enriquez-de-Salamanca M et al (2012) Amerindians show no association of PC-1 gene Gln121 allele and obesity: a thrifty gene population genetics. Mol Biol Rep 39:7687–7693PubMedCrossRefGoogle Scholar
  9. 9.
    Ukkola O, Ravussin E, Jacobson P, Sjostrom L, Bouchard C (2003) Mutations in the adiponectin gene in lean and obese subjects from the Swedish obese subjects cohort. Metabolism 52:881–884PubMedCrossRefGoogle Scholar
  10. 10.
    Beebe-Dimmer JL, Zuhlke KA, Ray AM, Lange EM, Cooney KA (2010) Genetic variation in adiponectin (ADIPOQ) and the type 1 receptor (ADIPOR1), obesity and prostate cancer in African Americans. Prostate Cancer Prostatic Dis 13:362–368PubMedCrossRefGoogle Scholar
  11. 11.
    Ranjith N, Pegoraro RJ, Shanmugam R (2011) Obesity-associated genetic variants in young Asian Indians with the metabolic syndrome and myocardial infarction. Cardiovasc J Afr 22:25–30PubMedCrossRefGoogle Scholar
  12. 12.
    World Health Organization (2004) Public health nutrition, volume 7, number 1A, supplement 1001. World Health Organization, GenevaGoogle Scholar
  13. 13.
    World Health Organization (2008) The global burden of disease: 2004 update. World Health Organization, GenevaGoogle Scholar
  14. 14.
    Takahashi M, Arita Y, Yamagata K, Matsukawa Y, Okutomi K, Horie M et al (2000) Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord 24:861–868PubMedCrossRefGoogle Scholar
  15. 15.
    Gonzalez-Sanchez JL, Zabena CA, Martinez-Larrad MT, Fernandez-Perez C, Perez-Barba M, Laakso M et al (2005) An SNP in the adiponectin gene is associated with decreased serum adiponectin levels and risk for impaired glucose tolerance. Obes Res 13:807–812PubMedCrossRefGoogle Scholar
  16. 16.
    Fumeron F, Aubert R, Siddiq A, Betoulle D, Pean F, Hadjadj S et al (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 53:1150–1157PubMedCrossRefGoogle Scholar
  17. 17.
    Sun H, Gong ZC, Yin JY, Liu HL, Liu YZ, Guo ZW et al (2008) The association of adiponectin allele 45T/G and −11377C/G polymorphisms with Type 2 diabetes and rosiglitazone response in Chinese patients. Br J Clin Pharmacol 65:917–926PubMedCrossRefGoogle Scholar
  18. 18.
    Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K et al (2002) Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 51:536–540PubMedCrossRefGoogle Scholar
  19. 19.
    Melistas L, Mantzoros CS, Kontogianni M, Antonopoulou S, Ordovas JM, Yiannakouris N (2009) Association of the +45T>G and +276G>T polymorphisms in the adiponectin gene with insulin resistance in nondiabetic Greek women. Eur J Endocrinol 161:845–852PubMedCrossRefGoogle Scholar
  20. 20.
    Huang MC, Wang TN, Lee KT, Wu YJ, Tu HP, Liu CS et al (2010) Adiponectin gene SNP276 variants and central obesity confer risks for hyperglycemia in indigenous Taiwanese. Kaohsiung J Med Sci 26:227–236PubMedCrossRefGoogle Scholar
  21. 21.
    Wang Y, Zhang D, Liu Y, Yang Y, Zhao T, Xu J et al (2009) Association study of the single nucleotide polymorphisms in adiponectin-associated genes with type 2 diabetes in Han Chinese. J Genet Genomics 36:417–423PubMedCrossRefGoogle Scholar
  22. 22.
    Potapov VA, Chistiakov DA, Dubinina A, Shamkhalova MS, Shestakova MV, Nosikov VV (2008) Adiponectin and adiponectin receptor gene variants in relation to type 2 diabetes and insulin resistance-related phenotypes. Rev Diabet Stud 5:28–37PubMedCrossRefGoogle Scholar
  23. 23.
    Al Daghri NM, Al Attas OS, Alokail MS, Alkharfy KM, Hussain T, Yakout S et al (2012) Adiponectin gene polymorphisms (T45G and G276T), adiponectin levels and risk for metabolic diseases in an Arab population. Gene 493:142–147PubMedCrossRefGoogle Scholar
  24. 24.
    Lionetti L, Mollica MP, Lombardi A, Cavaliere G, Gifuni G, Barletta A (2009) From chronic overnutrition to insulin resistance: the role of fat-storing capacity and inflammation. Nutr Metab Cardiovasc Dis 19:146–152PubMedCrossRefGoogle Scholar
  25. 25.
    Parga-Lozano C, Rey-Medrano D, Gomez-Prieto P, Areces C, Moscoso J, Abd-El-Fatah-Khalil S et al (2011) HLA genes in Amerindian immigrants to Madrid (Spain): epidemiology and a virtual transplantation waiting list: Amerindians in Madrid (Spain). Mol Biol Rep 38:2263–2271PubMedCrossRefGoogle Scholar
  26. 26.
    Arnaiz-Villena A, Parga-Lozano C, Moreno E, Areces C, Rey D, Gomez-Prieto P (2010) The origin of Amerindians and the peopling of the Americas according to HLA genes: admixture with Asian and Pacific people. Curr Genomics 11:103–114PubMedCrossRefGoogle Scholar
  27. 27.
    Neel JV (1962) Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Am J Hum Genet 14:353–362PubMedGoogle Scholar
  28. 28.
    Ewald PW (2008) An evolutionary perspective on the causes of chronic diseases: atherosclerosis. In: Evolutionary medicine and health, Oxford University Press, New York, pp 350–367Google Scholar
  29. 29.
    Szopa M, Malczewska-Malec M, Kiec-Wilk B, Skupien J, Wolkow P, Malecki MT et al (2009) Variants of the adiponectin gene and type 2 diabetes in a Polish population. Acta Diabetol 46:317–322PubMedCrossRefGoogle Scholar
  30. 30.
    Mousavinasab F, Tahtinen T, Jokelainen J, Koskela P, Vanhala M, Oikarinen J et al (2006) Common polymorphisms (single-nucleotide polymorphisms SNP+45 and SNP+276) of the adiponectin gene regulate serum adiponectin concentrations and blood pressure in young Finnish men. Mol Genet Metab 87:147–151PubMedCrossRefGoogle Scholar
  31. 31.
    Mackevics V, Heid IM, Wagner SA, Cip P, Doppelmayr H, Lejnieks A et al (2006) The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians. Eur J Hum Genet 14:349–356PubMedCrossRefGoogle Scholar
  32. 32.
    Fang WL, Zhou B, Wang YY, Chen Y, Zhang L (2010) Analysis of adiponectin gene polymorphisms in Chinese population with systemic lupus erythematosus. J Biomed Biotechnol 2010:401537PubMedCrossRefGoogle Scholar
  33. 33.
    Namvaran F, Azarpira N, Geramizadeh B, Rahimi-Moghaddam P (2011) Distribution and genotype frequency of adiponectin (+45 T/G) and adiponectin receptor2 (+795 G/A) single nucleotide polymorphisms in Iranian population. Gene 486:97–103PubMedCrossRefGoogle Scholar
  34. 34.
    Kang ES, Park SY, Kim HJ, Ahn CW, Nam M, Cha BS et al (2005) The influence of adiponectin gene polymorphism on the rosiglitazone response in patients with type 2 diabetes. Diabetes Care 28:1139–1144PubMedCrossRefGoogle Scholar
  35. 35.
    Panidis D, Kourtis A, Kukuvitis A, Farmakiotis D, Xita N, Georgiou I et al (2004) Association of the T45G polymorphism in exon 2 of the adiponectin gene with polycystic ovary syndrome: role of Delta4-androstenedione. Hum Reprod 19:1728–1733PubMedCrossRefGoogle Scholar
  36. 36.
    Li LL, Kang XL, Ran XJ, Wang Y, Wang CH, Huang L et al (2007) Associations between 45T/G polymorphism of the adiponectin gene and plasma adiponectin levels with type 2 diabetes. Clin Exp Pharmacol Physiol 34:1287–1290PubMedCrossRefGoogle Scholar
  37. 37.
    Kaklamani VG, Wisinski KB, Sadim M, Gulden C, Do A, Offit K et al (2008) Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk. JAMA 300:1523–1531PubMedCrossRefGoogle Scholar
  38. 38.
    Khabour OF, Mesmar FS, Alatoum MA, Gharaibeh MY, Alzoubi KH (2010) Associations of polymorphisms in adiponectin and leptin genes with men’s longevity. Aging Male 13:188–193PubMedCrossRefGoogle Scholar
  39. 39.
    The International HapMap Consortium (2012) International HapMap project. Accessed 10 July 2012
  40. 40.
    Chang YC, Jiang JY, Jiang YD, Chiang FT, Hwang JJ, Lien WP et al (2009) Interaction of ADIPOQ genetic polymorphism with blood pressure and plasma cholesterol level on the risk of coronary artery disease. Circ J 73:1934–1938PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Antonio Arnaiz-Villena
    • 1
    Email author
  • Mercedes Fernández-Honrado
    • 2
  • Diego Rey
    • 1
  • Mercedes Enríquez-de-Salamanca
    • 1
  • Sedeka Abd-El-Fatah-Khalil
    • 2
  • Ignacio Arribas
    • 3
  • Carmen Coca
    • 3
  • Manuel Algora
    • 2
  • Cristina Areces
    • 1
  1. 1.Department of ImmunologyThe Madrid Regional Blood Center, Facultad de Medicina, University ComplutenseMadridSpain
  2. 2.Department of HaematologyThe Madrid Regional Blood CenterMadridSpain
  3. 3.Department of BiochemistryHospital Príncipe de Asturias, Alcalá de HenaresMadridSpain

Personalised recommendations