BACKGROUND: Essential hypertension is associated with mitochondrial dysfunction. Because mitochondrial dynamics; mitochondrial morphological changes are closely linked with various mitochondrial functions, we aimed to examine whether the genetic variation of the mitochondria-shaping genes influenced the susceptibility to blood pressure (BP) and hypertension. METHODS: The quantitative BP trait analysis and hypertension case-control analysis for the total 52 single-nucleotide polymorphisms (SNPs) in the five major mitochondria-shaping genes were performed in the Korean Association Resource (KARE) study cohort (8,512 subjects). RESULTS: In the total subjects of the KARE study cohort, there were no statistically significant associations of the SNPs in the five mitochondria-shaping genes with BP or hypertension after adjusting for multiple tests. However, the age group analysis in the 40s, 50s, and 60s age subgroups revealed that 15 SNPs out of 26 SNPs genotyped in the OPA1 gene were significantly associated with BP and/or hypertension in the 60s age subgroup and their association P values satisfied the Bonferroni-corrected significance level (P < 0.00625). Noticeably, nine SNPs were consistently associated with all the three traits; systolic BP (SBP), diastolic BP (DBP), and hypertension. In silico lookup of the associated SNPs in the Southern German population did not reveal associations with BP traits. CONCLUSIONS: Our results indicate that genetic variation of the mitochondrial fusion-regulating gene, OPA1, might be associated with BP and hypertension in an age-dependent and population-specific manner in the Korean study cohort, and suggest that altered mitochondrial dynamics, especially involved in the mitochondrial fusion event, may play an important role in the pathogenesis of hypertension.
BACKGROUND: Essential hypertension is associated with mitochondrial dysfunction. Because mitochondrial dynamics; mitochondrial morphological changes are closely linked with various mitochondrial functions, we aimed to examine whether the genetic variation of the mitochondria-shaping genes influenced the susceptibility to blood pressure (BP) and hypertension. METHODS: The quantitative BP trait analysis and hypertension case-control analysis for the total 52 single-nucleotide polymorphisms (SNPs) in the five major mitochondria-shaping genes were performed in the Korean Association Resource (KARE) study cohort (8,512 subjects). RESULTS: In the total subjects of the KARE study cohort, there were no statistically significant associations of the SNPs in the five mitochondria-shaping genes with BP or hypertension after adjusting for multiple tests. However, the age group analysis in the 40s, 50s, and 60s age subgroups revealed that 15 SNPs out of 26 SNPs genotyped in the OPA1 gene were significantly associated with BP and/or hypertension in the 60s age subgroup and their association P values satisfied the Bonferroni-corrected significance level (P < 0.00625). Noticeably, nine SNPs were consistently associated with all the three traits; systolic BP (SBP), diastolic BP (DBP), and hypertension. In silico lookup of the associated SNPs in the Southern German population did not reveal associations with BP traits. CONCLUSIONS: Our results indicate that genetic variation of the mitochondrial fusion-regulating gene, OPA1, might be associated with BP and hypertension in an age-dependent and population-specific manner in the Korean study cohort, and suggest that altered mitochondrial dynamics, especially involved in the mitochondrial fusion event, may play an important role in the pathogenesis of hypertension.
Authors: Jeannette Simino; Gang Shi; Joshua C Bis; Daniel I Chasman; Georg B Ehret; Xiangjun Gu; Xiuqing Guo; Shih-Jen Hwang; Eric Sijbrands; Albert V Smith; Germaine C Verwoert; Jennifer L Bragg-Gresham; Gemma Cadby; Peng Chen; Ching-Yu Cheng; Tanguy Corre; Rudolf A de Boer; Anuj Goel; Toby Johnson; Chiea-Chuen Khor; Carla Lluís-Ganella; Jian'an Luan; Leo-Pekka Lyytikäinen; Ilja M Nolte; Xueling Sim; Siim Sõber; Peter J van der Most; Niek Verweij; Jing Hua Zhao; Najaf Amin; Eric Boerwinkle; Claude Bouchard; Abbas Dehghan; Gudny Eiriksdottir; Roberto Elosua; Oscar H Franco; Christian Gieger; Tamara B Harris; Serge Hercberg; Albert Hofman; Alan L James; Andrew D Johnson; Mika Kähönen; Kay-Tee Khaw; Zoltan Kutalik; Martin G Larson; Lenore J Launer; Guo Li; Jianjun Liu; Kiang Liu; Alanna C Morrison; Gerjan Navis; Rick Twee-Hee Ong; George J Papanicolau; Brenda W Penninx; Bruce M Psaty; Leslie J Raffel; Olli T Raitakari; Kenneth Rice; Fernando Rivadeneira; Lynda M Rose; Serena Sanna; Robert A Scott; David S Siscovick; Ronald P Stolk; Andre G Uitterlinden; Dhananjay Vaidya; Melanie M van der Klauw; Ramachandran S Vasan; Eranga Nishanthie Vithana; Uwe Völker; Henry Völzke; Hugh Watkins; Terri L Young; Tin Aung; Murielle Bochud; Martin Farrall; Catharina A Hartman; Maris Laan; Edward G Lakatta; Terho Lehtimäki; Ruth J F Loos; Gavin Lucas; Pierre Meneton; Lyle J Palmer; Rainer Rettig; Harold Snieder; E Shyong Tai; Yik-Ying Teo; Pim van der Harst; Nicholas J Wareham; Cisca Wijmenga; Tien Yin Wong; Myriam Fornage; Vilmundur Gudnason; Daniel Levy; Walter Palmas; Paul M Ridker; Jerome I Rotter; Cornelia M van Duijn; Jacqueline C M Witteman; Aravinda Chakravarti; Dabeeru C Rao Journal: Am J Hum Genet Date: 2014-06-19 Impact factor: 11.025