AIM: Previous studies suggest that klotho gene polymorphisms may be associated with atherosclerosis, but did not assess the relationship between klotho gene polymorphisms and atherosclerosis parameters such as carotid artery intima-media thickness (IMT). Here, we studied whether klotho single nucleotide polymorphisms (SNP) were associated with carotid atherosclerosis. METHODS: All subjects were Japanese. Eight-hundred and fifty-three patients with hypertension (465 men and 388 women) in the outpatient clinic and 1783 subjects from the general population (821 men and 962 women) attending health check-ups were analyzed in the present study. We measured mean IMT of the common carotid artery to evaluate carotid atherosclerosis. Four single nucleotide polymorphisms (SNP) (rs7323281; intron1, rs5644481; exon4, rs3752472; exon3, rs650439; intron4) of klotho were selected as representative SNP in haplotype blocks. RESULTS: Multivariate logistic regression analysis adjusted by confounding factors showed a significant association of rs650439 with carotid atherosclerosis in hypertensive patients (TT vs TA vs AA, P < 0.01; TT + TA vs AA, P < 0.01). By ancova considering confounding factors, rs650439 was also significantly associated with mean IMT (TT + TA vs AA, P = 0.04) in the hypertensive population. However, there was no significant association between klotho SNP and carotid IMT in the general population. Compared to the general population, the subject group with hypertensive patients clearly had more atherosclerosis risk factors. CONCLUSION: Only in hypertensive patients was klotho rs650439 strongly associated with mean IMT thickening of the common carotid artery. Therefore, klotho SNP (rs650439) may influence on the progression of carotid atherosclerosis in patients with hypertension.
AIM: Previous studies suggest that klotho gene polymorphisms may be associated with atherosclerosis, but did not assess the relationship between klotho gene polymorphisms and atherosclerosis parameters such as carotid artery intima-media thickness (IMT). Here, we studied whether klotho single nucleotide polymorphisms (SNP) were associated with carotid atherosclerosis. METHODS: All subjects were Japanese. Eight-hundred and fifty-three patients with hypertension (465 men and 388 women) in the outpatient clinic and 1783 subjects from the general population (821 men and 962 women) attending health check-ups were analyzed in the present study. We measured mean IMT of the common carotid artery to evaluate carotid atherosclerosis. Four single nucleotide polymorphisms (SNP) (rs7323281; intron1, rs5644481; exon4, rs3752472; exon3, rs650439; intron4) of klotho were selected as representative SNP in haplotype blocks. RESULTS: Multivariate logistic regression analysis adjusted by confounding factors showed a significant association of rs650439 with carotid atherosclerosis in hypertensivepatients (TT vs TA vs AA, P < 0.01; TT + TA vs AA, P < 0.01). By ancova considering confounding factors, rs650439 was also significantly associated with mean IMT (TT + TA vs AA, P = 0.04) in the hypertensive population. However, there was no significant association between klotho SNP and carotid IMT in the general population. Compared to the general population, the subject group with hypertensivepatients clearly had more atherosclerosis risk factors. CONCLUSION: Only in hypertensivepatients was klothors650439 strongly associated with mean IMT thickening of the common carotid artery. Therefore, klotho SNP (rs650439) may influence on the progression of carotid atherosclerosis in patients with hypertension.
Authors: Javier Donate-Correa; Carla M Ferri; Ernesto Martín-Núñez; Nayra Pérez-Delgado; Ainhoa González-Luis; Carmen Mora-Fernández; Juan F Navarro-González Journal: Sci Rep Date: 2021-08-05 Impact factor: 4.379
Authors: Robert A Scott; Vasiliki Lagou; Ryan P Welch; Eleanor Wheeler; May E Montasser; Jian'an Luan; Reedik Mägi; Rona J Strawbridge; Emil Rehnberg; Stefan Gustafsson; Stavroula Kanoni; Laura J Rasmussen-Torvik; Loïc Yengo; Cecile Lecoeur; Dmitry Shungin; Serena Sanna; Carlo Sidore; Paul C D Johnson; J Wouter Jukema; Toby Johnson; Anubha Mahajan; Niek Verweij; Gudmar Thorleifsson; Jouke-Jan Hottenga; Sonia Shah; Albert V Smith; Bengt Sennblad; Christian Gieger; Perttu Salo; Markus Perola; Nicholas J Timpson; David M Evans; Beate St Pourcain; Ying Wu; Jeanette S Andrews; Jennie Hui; Lawrence F Bielak; Wei Zhao; Momoko Horikoshi; Pau Navarro; Aaron Isaacs; Jeffrey R O'Connell; Kathleen Stirrups; Veronique Vitart; Caroline Hayward; Tõnu Esko; Evelin Mihailov; Ross M Fraser; Tove Fall; Benjamin F Voight; Soumya Raychaudhuri; Han Chen; Cecilia M Lindgren; Andrew P Morris; Nigel W Rayner; Neil Robertson; Denis Rybin; Ching-Ti Liu; Jacques S Beckmann; Sara M Willems; Peter S Chines; Anne U Jackson; Hyun Min Kang; Heather M Stringham; Kijoung Song; Toshiko Tanaka; John F Peden; Anuj Goel; Andrew A Hicks; Ping An; Martina Müller-Nurasyid; Anders Franco-Cereceda; Lasse Folkersen; Letizia Marullo; Hanneke Jansen; Albertine J Oldehinkel; Marcel Bruinenberg; James S Pankow; Kari E North; Nita G Forouhi; Ruth J F Loos; Sarah Edkins; Tibor V Varga; Göran Hallmans; Heikki Oksa; Mulas Antonella; Ramaiah Nagaraja; Stella Trompet; Ian Ford; Stephan J L Bakker; Augustine Kong; Meena Kumari; Bruna Gigante; Christian Herder; Patricia B Munroe; Mark Caulfield; Jula Antti; Massimo Mangino; Kerrin Small; Iva Miljkovic; Yongmei Liu; Mustafa Atalay; Wieland Kiess; Alan L James; Fernando Rivadeneira; Andre G Uitterlinden; Colin N A Palmer; Alex S F Doney; Gonneke Willemsen; Johannes H Smit; Susan Campbell; Ozren Polasek; Lori L Bonnycastle; Serge Hercberg; Maria Dimitriou; Jennifer L Bolton; Gerard R Fowkes; Peter Kovacs; Jaana Lindström; Tatijana Zemunik; Stefania Bandinelli; Sarah H Wild; Hanneke V Basart; Wolfgang Rathmann; Harald Grallert; Winfried Maerz; Marcus E Kleber; Bernhard O Boehm; Annette Peters; Peter P Pramstaller; Michael A Province; Ingrid B Borecki; Nicholas D Hastie; Igor Rudan; Harry Campbell; Hugh Watkins; Martin Farrall; Michael Stumvoll; Luigi Ferrucci; Dawn M Waterworth; Richard N Bergman; Francis S Collins; Jaakko Tuomilehto; Richard M Watanabe; Eco J C de Geus; Brenda W Penninx; Albert Hofman; Ben A Oostra; Bruce M Psaty; Peter Vollenweider; James F Wilson; Alan F Wright; G Kees Hovingh; Andres Metspalu; Matti Uusitupa; Patrik K E Magnusson; Kirsten O Kyvik; Jaakko Kaprio; Jackie F Price; George V Dedoussis; Panos Deloukas; Pierre Meneton; Lars Lind; Michael Boehnke; Alan R Shuldiner; Cornelia M van Duijn; Andrew D Morris; Anke Toenjes; Patricia A Peyser; John P Beilby; Antje Körner; Johanna Kuusisto; Markku Laakso; Stefan R Bornstein; Peter E H Schwarz; Timo A Lakka; Rainer Rauramaa; Linda S Adair; George Davey Smith; Tim D Spector; Thomas Illig; Ulf de Faire; Anders Hamsten; Vilmundur Gudnason; Mika Kivimaki; Aroon Hingorani; Sirkka M Keinanen-Kiukaanniemi; Timo E Saaristo; Dorret I Boomsma; Kari Stefansson; Pim van der Harst; Josée Dupuis; Nancy L Pedersen; Naveed Sattar; Tamara B Harris; Francesco Cucca; Samuli Ripatti; Veikko Salomaa; Karen L Mohlke; Beverley Balkau; Philippe Froguel; Anneli Pouta; Marjo-Riitta Jarvelin; Nicholas J Wareham; Nabila Bouatia-Naji; Mark I McCarthy; Paul W Franks; James B Meigs; Tanya M Teslovich; Jose C Florez; Claudia Langenberg; Erik Ingelsson; Inga Prokopenko; Inês Barroso Journal: Nat Genet Date: 2012-08-12 Impact factor: 38.330
Authors: Kenneth Lim; Arnoud Groen; Guerman Molostvov; Tzongshi Lu; Kathryn S Lilley; David Snead; Sean James; Ian B Wilkinson; Stephen Ting; Li-Li Hsiao; Thomas F Hiemstra; Daniel Zehnder Journal: J Clin Endocrinol Metab Date: 2015-08-17 Impact factor: 5.958