title: Associations of Variants in the CACNA1A and CACNA1C Genes With Longitudinal Blood Pressure Changes and Hypertension Incidence: The GenSalt Study.
abstract: We aimed to examine the associations of voltage-dependent calcium-channel genes CACNA1A and CACNA1C with blood pressure (BP) changes and hypertension incidence in a longitudinal family study.
  
  
  
  A total of 1,768 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were eligible for the current study. Nine BP measurements were obtained at baseline and each follow-up visit using a random-zero sphygmomanometer. Mixed-effect models were used to assess additive associations of 176 tag single-nucleotide polymorphisms (SNPs) in CACNA1A and CACNA1C with longitudinal BP changes and hypertension incidence. The truncated product method was used for gene-based analysis. The Bonferroni correction was used for adjustment of multiple testing.
  
  
  
  During an average of 7.2 years of follow-up, 512 (32.1%) participants developed hypertension. CACNA1A SNP rs8182538 was significantly associated with longitudinal diastolic BP (DBP) change after Bonferroni correction ( Pinteraction = 9.90×10 -5 ), with mean DBP increases of 0.85, 1.03, and 1.19mm Hg per year for participants with genotypes C/C , C/T , and T/T , respectively. A similar trend was observed for the association of rs8182538 with systolic BP (SBP) change. In the gene-based analysis, CACNA1A and CACNA1C were significantly associated with DBP change ( P = 2.0×10 -5 ) and SBP change ( P = 1.4×10 -4 ) after Bonferroni correction, respectively. The gene-based associations remained significant after removing rs8182538 within CACNA1A and rs758116 within CACNA1C in sensitivity analysis.
  
  
  
  Our findings indicated that CACNA1A and CACNA1C might contribute to BP changes over time in Han Chinese population. Further replication of these findings is warranted.
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Zunsong
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Fangchao
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Mengting
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.|Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Huang
authors.affiliation: Division of Biostatistics, Washington University School of Medicine , St. Louis, Missouri , USA.
authors.forename: Dabeeru C
authors.initials: DC
authors.lastname: Rao
authors.affiliation: Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health , Houston, Texas , USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
authors.affiliation: Division of Biostatistics, Washington University School of Medicine , St. Louis, Missouri , USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine , New Orleans, Louisiana , USA.
authors.forename: Tanika N
authors.initials: TN
authors.lastname: Kelly
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Xueli
authors.initials: X
authors.lastname: Yang
mesh_terms: D001794:Blood Pressure; D001795:Blood Pressure Determination; D015220:Calcium Channels / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000235:genetics; D002681:China; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D015994:Incidence; D020641:Polymorphism, Single Nucleotide; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C079146:CACNA1C protein, human