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Association between BBS6/MKKS gene polymorphisms, obesity and metabolic syndrome in the Greek population

International Journal of Obesity volume 32, pages 1618–1625 (2008)Cite this article

Abstract

Objective:

To investigate the relationship between MKKS gene variations, obesity-related traits and features of the metabolic syndrome (MS) in the Greek population.

Design and subjects:

Genotype and haplotype analysis was carried out for six known MKKS gene polymorphisms (534C>T, 985+16T>G, 985+33C>G, 986−29A>T, 1161+58A>G and 1595G>T) in 220 obese subjects (body mass index ⩾30 kg/m2) and 330 non-obese controls.

Results:

Genotype frequencies of the 985+16T>G, 986−29A>T and 1595G>T SNPs were significantly different between obese and non-obese individuals (P=0.0016, 0.0196 and 0.0069, respectively). Obese carriers of the risk alleles of the above three polymorphisms had a significantly increased prevalence of arterial hypertension. Furthermore, obese carriers of the G allele for the 985+16T>G polymorphism had an increased prevalence of type 2 diabetes mellitus and of MS component traits. A new polymorphism was detected, namely a C to T substitution at position 1129 (1129C>T or N377N). Frequency of the T allele for the 1129C>T polymorphism was significantly higher in control individuals than in obese subjects (P=0.0253). Haplotype TGTGT was more prevalent in obese than in controls (P=0.0002) and was associated with increased prevalence of the MS in obese subjects (P<0.0001).

Conclusion:

Our results suggest that genetic variation in the MKKS gene may play a role in the development of obesity and the metabolic syndrome.

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References

  1. Perusse L, Bouchard C . Genotype-environment interaction in human obesity. Nutr Rev 1999; 57: S31–S37; discussion S37–S38.

    Article  CAS  Google Scholar 

  2. Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring) 2006; 14: 529–644.

    Article  Google Scholar 

  3. Blacque OE, Leroux MR . Bardet–Biedl syndrome: an emerging pathomechanism of intracellular transport. Cell Mol Life Sci 2006; 63: 2145–2161.

    Article  CAS  Google Scholar 

  4. Beales PL . Lifting the lid on Pandora's box: the Bardet–Biedl syndrome. Curr Opin Genet Dev 2005; 15: 315–323.

    Article  CAS  Google Scholar 

  5. Forti E, Aksanov O, Birk RZ . Temporal expression pattern of Bardet–Biedl syndrome genes in adipogenesis. Int J Biochem Cell Biol 2007; 39: 1055–1062.

    Article  CAS  Google Scholar 

  6. Croft JB, Morrell D, Chase CL, Swift M . Obesity in heterozygous carriers of the gene for the Bardet–Biedl syndrome. Am J Med Genet 1995; 55: 12–15.

    Article  CAS  Google Scholar 

  7. Stone DL, Agarwala R, Schaffer AA, Weber JL, Vaske D, Oda T et al. Genetic and physical mapping of the McKusick–Kaufman syndrome. Hum Mol Genet 1998; 7: 475–481.

    Article  CAS  Google Scholar 

  8. Slavotinek AM, Stone EM, Mykytyn K, Heckenlively JR, Green JS, Heon E et al. Mutations in MKKS cause Bardet–Biedl syndrome. Nat Genet 2000; 26: 15–16.

    Article  CAS  Google Scholar 

  9. Katsanis N, Beales PL, Woods MO, Lewis RA, Green JS, Parfrey PS et al. Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet–Biedl syndrome. Nat Genet 2000; 26: 67–70.

    Article  CAS  Google Scholar 

  10. Fath MA, Mullins RF, Searby C, Nishimura DY, Wei J, Rahmouni K et al. Mkks-null mice have a phenotype resembling Bardet–Biedl syndrome. Hum Mol Genet 2005; 14: 1109–1118.

    Article  CAS  Google Scholar 

  11. Andersen KL, Echwald SM, Larsen LH, Hamid YH, Glumer C, Jorgensen T et al. Variation of the McKusick–Kaufman gene and studies of relationships with common forms of obesity. J Clin Endocrinol Metab 2005; 90: 225–230.

    Article  CAS  Google Scholar 

  12. Benzinou M, Walley A, Lobbens S, Charles MA, Jouret B, Fumeron F et al. Bardet–Biedl syndrome gene variants are associated with both childhood and adult common obesity in French Caucasians. Diabetes 2006; 55: 2876–2882.

    Article  CAS  Google Scholar 

  13. Iannello S, Bosco P, Cavaleri A, Camuto M, Milazzo P, Belfiore F . A review of the literature of Bardet–Biedl disease and report of three cases associated with metabolic syndrome and diagnosed after the age of fifty. Obes Rev 2002; 3: 123–135.

    Article  CAS  Google Scholar 

  14. Scott EM, Carter AM, Grant PJ . Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man. Int J Obes (Lond) 2008; 32: 658–662.

    Article  CAS  Google Scholar 

  15. Wiedmann S, Fischer M, Koehler M, Neureuther K, Riegger G, Doering A et al. Genetic variants within the LPIN1 gene, encoding lipin, are influencing phenotypes of the metabolic syndrome in humans. Diabetes 2008; 57: 209–217.

    Article  CAS  Google Scholar 

  16. Sanchez-Corona J, Flores-Martinez SE, Machorro-Lazo MV, Galaviz-Hernandez C, Moran-Moguel MC, Perea FJ et al. Polymorphisms in candidate genes for type 2 diabetes mellitus in a Mexican population with metabolic syndrome findings. Diabetes Res Clin Pract 2004; 63: 47–55.

    Article  CAS  Google Scholar 

  17. Yu K, Wang Z, Li Q, Wacholder S, Hunter DJ, Hoover RN et al. Population substructure and control selection in genome-wide association studies. PLoS ONE 2008; 3: e2551.

    Article  Google Scholar 

  18. Kondopoulou H, Loftus R, Kouvatsi A, Triantaphyllidis C . Genetic studies in 5 Greek population samples using 12 highly polymorphic DNA loci. Hum Biol 1999; 71: 27–42.

    CAS  PubMed  Google Scholar 

  19. Kouvatsi A, Karaiskou N, Apostolidis A, Kirmizidis G . Mitochondrial DNA sequence variation in Greeks. Hum Biol 2001; 73: 855–869.

    Article  CAS  Google Scholar 

  20. World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation on obesity, Geneva, 3-5 June 1997. World Health Organization: Geneva, 1998.

  21. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112: 2735–2752.

    Article  Google Scholar 

  22. International Diabetes Federation (IDF). The IDF consensus worldwide definition of the metabolic syndrome. Part 1. Worldwide definition for use in clinical practice, 2006.

  23. Sambrook J, Russell DW . Molecular cloning: a laboratory manual, 3rd edn, Cold Spring Harbor Laboratory Press: Cold Spring Harbor, New York, 2001.

    Google Scholar 

  24. Untergasser A, Nijveen JI, Rao X, Bisseling T, Geurts R, Leunissen JA . Primer3Plus, an enhanced web interface to Primer3. Nucleic Acids Res 2007; 35: W71–W74.

    Article  Google Scholar 

  25. Rust S, Funke H, Assmann G . Mutagenically separated PCR (MS-PCR): a highly specific one step procedure for easy mutation detection. Nucleic Acids Res 1993; 21: 3623–3629.

    Article  CAS  Google Scholar 

  26. Raymond M, Rousset F . GENEPOP (v3.1): population genetics software for exact tests and ecumenicism. J Hered 1995; 86: 248–249.

    Article  Google Scholar 

  27. Tregouet DA, Garelle V . A new JAVA interface implementation of THESIAS: testing haplotype effects in association studies. Bioinformatics 2007; 23: 1038–1039.

    Article  CAS  Google Scholar 

  28. Hall TA . BIOEDIT: a user-friendly biological sequence alignment editor and analysis program for windows 95/98/NT. Nucleic Acids Symp Ser 1999; 41: 95–98.

    CAS  Google Scholar 

  29. Yuan HY, Chiou JJ, Tseng WH, Liu CH, Liu CK, Lin YJ et al. FASTSNP: an always up-to-date and extendable service for SNP function analysis and prioritization. Nucleic Acids Res 2006; 34: W635–W641.

    Article  CAS  Google Scholar 

  30. Rice WR . Analyzing tables of statistical tests. Evolution 1989; 43: 223–225.

    Article  Google Scholar 

  31. Lavebratt C, Alpman A, Persson B, Arner P, Hoffstedt J . Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men. Int J Obes (Lond) 2006; 30: 453–459.

    Article  CAS  Google Scholar 

  32. Geller F, Reichwald K, Dempfle A, Illig T, Vollmert C, Herpertz S et al. Melanocortin-4 receptor gene variant I103 is negatively associated with obesity. Am J Hum Genet 2004; 74: 572–581.

    Article  CAS  Google Scholar 

  33. Athyros VG, Bouloukos VI, Pehlivanidis AN, Papageorgiou AA, Dionysopoulou SG, Symeonidis AN et al. The prevalence of the metabolic syndrome in Greece: the MetS-Greece Multicentre Study. Diabetes Obes Metab 2005; 7: 397–405.

    Article  CAS  Google Scholar 

  34. Psaltopoulou T, Orfanos P, Naska A, Lenas D, Trichopoulos D, Trichopoulou A . Prevalence, awareness, treatment and control of hypertension in a general population sample of 26,913 adults in the Greek EPIC study. Int J Epidemiol 2004; 33: 1345–1352.

    Article  Google Scholar 

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Acknowledgements

All participating individuals in this study are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece,

    K Rouskas, A Kalogeridis & A Kouvatsi

  2. Second Medical Department, Metabolic Diseases Unit, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece

    K Paletas, M Sarigianni & A Tsapas

  3. Department of Hematology, Second Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece

    E Ioannidou-Papagiannaki

Authors
  1. K Rouskas
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  2. K Paletas
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  3. A Kalogeridis
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  4. M Sarigianni
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  5. E Ioannidou-Papagiannaki
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  6. A Tsapas
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  7. A Kouvatsi
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Correspondence to A Kouvatsi.

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Supplementary Information accompanies the paper on International Journal of Obesity website (http://www.nature.com/ijo)

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Rouskas, K., Paletas, K., Kalogeridis, A. et al. Association between BBS6/MKKS gene polymorphisms, obesity and metabolic syndrome in the Greek population. Int J Obes 32, 1618–1625 (2008). https://doi.org/10.1038/ijo.2008.167

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