OBJECTIVE: Cystatin C, a protein coded by CST3 gene, is implicated in adipose tissue biology. Our hypothesis is that common variants in CST3 gene could play a role in the development of corpulence during lifetime. METHODS: Two tag SNPs were selected to capture all SNPs in the CST3 region. We first investigated the association of the two tag SNPs individually and combined into haplotypes with corpulence related phenotypes in 4,288 French subjects (BMI = 24.31 ( 3.74 kg/m²). Significant findings were replicated in five independent populations--790 Danish lean men (BMI = 24.63 ( 2.30 kg/m²), 672 Danish obese men (BMI = 33.23 ( 2.34 kg/m²), 763 Swedish women (BMI = 21.73 ( 2.87 kg/m²), 1,848 Danish lean women (BMI = 22.66 ( 2.85 kg/m²) and 2,061 Danish obese women (BMI = 37.01 ( 3.59 kg/m²). RESULTS: Rs2424577 was associated with BMI in three independent populations--G/G carriers were less corpulent than A/A carriers in the French individuals (p = 0.045) and in the Danish lean men (p = 0.021), and they were more corpulent in the group of Swedish women (p = 0.004). This phenomenon has been described as a flip-flop phenomenon, probably caused by a multilocus effect. CONCLUSION: CST3 rs2424577 is associated with BMI in a complex fashion. This association is probably caused by the interaction between several functional variants.
OBJECTIVE: Cystatin C, a protein coded by CST3 gene, is implicated in adipose tissue biology. Our hypothesis is that common variants in CST3 gene could play a role in the development of corpulence during lifetime. METHODS: Two tag SNPs were selected to capture all SNPs in the CST3 region. We first investigated the association of the two tag SNPs individually and combined into haplotypes with corpulence related phenotypes in 4,288 French subjects (BMI = 24.31 ( 3.74 kg/m²). Significant findings were replicated in five independent populations--790 Danish lean men (BMI = 24.63 ( 2.30 kg/m²), 672 Danish obese men (BMI = 33.23 ( 2.34 kg/m²), 763 Swedish women (BMI = 21.73 ( 2.87 kg/m²), 1,848 Danish lean women (BMI = 22.66 ( 2.85 kg/m²) and 2,061 Danish obese women (BMI = 37.01 ( 3.59 kg/m²). RESULTS: Rs2424577 was associated with BMI in three independent populations--G/G carriers were less corpulent than A/A carriers in the French individuals (p = 0.045) and in the Danish lean men (p = 0.021), and they were more corpulent in the group of Swedish women (p = 0.004). This phenomenon has been described as a flip-flop phenomenon, probably caused by a multilocus effect. CONCLUSION: CST3 rs2424577 is associated with BMI in a complex fashion. This association is probably caused by the interaction between several functional variants.
Authors: F C Crawford; M J Freeman; J A Schinka; L I Abdullah; M Gold; R Hartman; K Krivian; M D Morris; D Richards; R Duara; R Anand; M J Mullan Journal: Neurology Date: 2000-09-26 Impact factor: 9.910
Authors: Elizabeth K Speliotes; Cristen J Willer; Sonja I Berndt; Keri L Monda; Gudmar Thorleifsson; Anne U Jackson; Hana Lango Allen; Cecilia M Lindgren; Jian'an Luan; Reedik Mägi; Joshua C Randall; Sailaja Vedantam; Thomas W Winkler; Lu Qi; Tsegaselassie Workalemahu; Iris M Heid; Valgerdur Steinthorsdottir; Heather M Stringham; Michael N Weedon; Eleanor Wheeler; Andrew R Wood; Teresa Ferreira; Robert J Weyant; Ayellet V Segrè; Karol Estrada; Liming Liang; James Nemesh; Ju-Hyun Park; Stefan Gustafsson; Tuomas O Kilpeläinen; Jian Yang; Nabila Bouatia-Naji; Tõnu Esko; Mary F Feitosa; Zoltán Kutalik; Massimo Mangino; Soumya Raychaudhuri; Andre Scherag; Albert Vernon Smith; Ryan Welch; Jing Hua Zhao; Katja K Aben; Devin M Absher; Najaf Amin; Anna L Dixon; Eva Fisher; Nicole L Glazer; Michael E Goddard; Nancy L Heard-Costa; Volker Hoesel; Jouke-Jan Hottenga; Asa Johansson; Toby Johnson; Shamika Ketkar; Claudia Lamina; Shengxu Li; Miriam F Moffatt; Richard H Myers; Narisu Narisu; John R B Perry; Marjolein J Peters; Michael Preuss; Samuli Ripatti; Fernando Rivadeneira; Camilla Sandholt; Laura J Scott; Nicholas J Timpson; Jonathan P Tyrer; Sophie van Wingerden; Richard M Watanabe; Charles C White; Fredrik Wiklund; Christina Barlassina; Daniel I Chasman; Matthew N Cooper; John-Olov Jansson; Robert W Lawrence; Niina Pellikka; Inga Prokopenko; Jianxin Shi; Elisabeth Thiering; Helene Alavere; Maria T S Alibrandi; Peter Almgren; Alice M Arnold; Thor Aspelund; Larry D Atwood; Beverley Balkau; Anthony J Balmforth; Amanda J Bennett; Yoav Ben-Shlomo; Richard N Bergman; Sven Bergmann; Heike Biebermann; Alexandra I F Blakemore; Tanja Boes; Lori L Bonnycastle; Stefan R Bornstein; Morris J Brown; Thomas A Buchanan; Fabio Busonero; Harry Campbell; Francesco P Cappuccio; Christine Cavalcanti-Proença; Yii-Der Ida Chen; Chih-Mei Chen; Peter S Chines; Robert Clarke; Lachlan Coin; John Connell; Ian N M Day; Martin den Heijer; Jubao Duan; Shah Ebrahim; Paul Elliott; Roberto Elosua; Gudny Eiriksdottir; 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Jan H Smit; Nicole Soranzo; Ulla Sovio; Jonathan Stephens; Ida Surakka; Amy J Swift; Mari-Liis Tammesoo; Jean-Claude Tardif; Maris Teder-Laving; Tanya M Teslovich; John R Thompson; Brian Thomson; Anke Tönjes; Tiinamaija Tuomi; Joyce B J van Meurs; Gert-Jan van Ommen; Vincent Vatin; Jorma Viikari; Sophie Visvikis-Siest; Veronique Vitart; Carla I G Vogel; Benjamin F Voight; Lindsay L Waite; Henri Wallaschofski; G Bragi Walters; Elisabeth Widen; Susanna Wiegand; Sarah H Wild; Gonneke Willemsen; Daniel R Witte; Jacqueline C Witteman; Jianfeng Xu; Qunyuan Zhang; Lina Zgaga; Andreas Ziegler; Paavo Zitting; John P Beilby; I Sadaf Farooqi; Johannes Hebebrand; Heikki V Huikuri; Alan L James; Mika Kähönen; Douglas F Levinson; Fabio Macciardi; Markku S Nieminen; Claes Ohlsson; Lyle J Palmer; Paul M Ridker; Michael Stumvoll; Jacques S Beckmann; Heiner Boeing; Eric Boerwinkle; Dorret I Boomsma; Mark J Caulfield; Stephen J Chanock; Francis S Collins; L Adrienne Cupples; George Davey Smith; Jeanette Erdmann; Philippe Froguel; Henrik Grönberg; Ulf Gyllensten; Per Hall; Torben Hansen; Tamara B Harris; Andrew T Hattersley; Richard B Hayes; Joachim Heinrich; Frank B Hu; Kristian Hveem; Thomas Illig; Marjo-Riitta Jarvelin; Jaakko Kaprio; Fredrik Karpe; Kay-Tee Khaw; Lambertus A Kiemeney; Heiko Krude; Markku Laakso; Debbie A Lawlor; Andres Metspalu; Patricia B Munroe; Willem H Ouwehand; Oluf Pedersen; Brenda W Penninx; Annette Peters; Peter P Pramstaller; Thomas Quertermous; Thomas Reinehr; Aila Rissanen; Igor Rudan; Nilesh J Samani; Peter E H Schwarz; Alan R Shuldiner; Timothy D Spector; Jaakko Tuomilehto; Manuela Uda; André Uitterlinden; Timo T Valle; Martin Wabitsch; Gérard Waeber; Nicholas J Wareham; Hugh Watkins; James F Wilson; Alan F Wright; M Carola Zillikens; Nilanjan Chatterjee; Steven A McCarroll; Shaun Purcell; Eric E Schadt; Peter M Visscher; Themistocles L Assimes; Ingrid B Borecki; Panos Deloukas; Caroline S Fox; Leif C Groop; Talin Haritunians; David J Hunter; Robert C Kaplan; Karen L Mohlke; 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Authors: Henri Hooton; Lars Angquist; Claus Holst; Jorg Hager; Francis Rousseau; Rikke D Hansen; Anne Tjønneland; Nina Roswall; Daphne L van der A; Kim Overvad; Marianne Uhre Jakobsen; Heiner Boeing; Karina Meidtner; Domenico Palli; Giovanna Masala; Nabila Bouatia-Naji; Wim H M Saris; Edith J M Feskens; Nicolas J Wareham; Karani S Vimaleswaran; Dominique Langin; Ruth J F Loos; Thorkild I A Sørensen; Karine Clément Journal: PLoS One Date: 2012-07-23 Impact factor: 3.240