Associations of the Serum/Glucocorticoid Regulated Kinase Genes With BP Changes and Hypertension Incidence: The Gensalt Study.
BACKGROUND
Single-marker and novel gene-based methods were employed to examine the associations of the serum/glucocorticoid regulated kinases (SGK) gene family with longitudinal blood pressure (BP) changes and hypertension incidence in a family-based cohort study.


METHODS
Totally, 1,768 Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were included in the current analyses. Nine BP measures were obtained at each of 3 visits during the GenSalt follow-up study. Mixed-model and Gene-based analyses were used to examine the associations of the SGK gene family with longitudinal BP phenotypes. Bonferroni correction was applied to account for multiple testing.


RESULTS
After an average 7.2-year follow-up, 32.2% (513) of participants free of hypertension at baseline developed hypertension. Four novel SNPs in the SGK1 gene were predictive of the longitudinal BP phenotypes. The major alleles of SGK1 rs1763498 and rs114414980 conferred 2.9- and 2.5-fold increased risks of hypertension development, respectively (P = 1.0×10-4and 6.0×10-4, respectively). In addition, the major allele of SGK1 rs229133 was significantly associated with 0.4mm Hg larger annual increases in systolic BP (P = 4.2×10-4), while the major allele of rs6924468 was significantly associated with 0.2mm Hg smaller annual increases in diastolic BP (P = 4.2×10-4). Gene-based analyses revealed an association of the SGK1 gene with risk of hypertension development (P = 7.4×10-3). No evidence for the SGK2 and SGK3 genes was found.


CONCLUSIONS
The findings of the current study suggest that the SGK1 gene may play a role in long-term BP regulation and hypertension incidence.
Department of Evidence Based Medicine, 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.|Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
Dingding
D
Zhang
Department of Evidence Based Medicine, 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.
Dongfeng
D
Gu
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
Jiang
J
He
Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas, USA.
James E
JE
Hixson
Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA.
Dabeeru C
DC
Rao
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
Changwei
C
Li
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
Hua
H
He
Department of Evidence Based Medicine, 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.
Jichun
J
Chen
Department of Evidence Based Medicine, 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.
Jianfeng
J
Huang
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
Jing
J
Chen
Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA.
Treva K
TK
Rice
Department of Evidence Based Medicine, 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.
Shufeng
S
Chen
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA; tkelly@tulane.edu.
Tanika N
TN
Kelly
D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D017874:Immediate-Early Proteins / Q000235:genetics*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases
SGK; blood pressure; blood pressure changes; common variants; hypertension.
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