title: Common variants in the Na(+)-coupled bicarbonate transporter genes and salt sensitivity of blood pressure: the GenSalt study.
abstract: The current study comprehensively examined the association between common variants in the Na(+)-coupled bicarbonate transporter (NCBT) genes and blood pressure (BP) responses to dietary sodium intervention. A 7-day low-sodium followed by a 7-day high-sodium dietary intervention was conducted among 1906 Han participants from rural areas of northern China. Nine BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. A mixed-effect model was used to assess the additive associations of 76 common variants in five NCBT genes, including SLC4A4, SLC4A5, SLC4A7, SLC4A8 and SLC4A10, with salt sensitivity phenotypes. The Bonferroni method was used to adjust for multiple testing. SLC4A4 marker rs4254735 was significantly associated with diastolic BP (DBP) response to low-sodium intervention (P=5.05 × 10(-4)), with mean (95% confidence interval (CI)) response of -2.91 (-3.21, -2.61) and -0.40 (-1.84, 1.05) mmHg for genotype AA and AG, respectively. In addition, BP responses to high-sodium intervention significantly increased with the number of minor C alleles of SLC4A4 marker rs10022637. Mean systolic BP responses among those with genotypes TT, CT and CC were 4.62 (4.29, 4.99), 5.94 (5.31, 6.58) and 6.00 (3.57, 8.43) mmHg (P=1.14 × 10(-4)); mean DBP responses were 1.72 (1.41, 2.03), 3.22 (2.52, 3.92) and 3.94 (1.88, 5.99) mmHg (P=2.26 × 10(-5)) and mean arterial pressure responses were 2.69 (2.40, 2.97), 4.13 (3.57, 4.70) and 4.61 (2.51, 6.71) mmHg (P=2.07 × 10(-6)), respectively. In brief, the present study indicated that common variants in the SLC4A4 gene might contribute to the variation of BP responses to dietary sodium intake in Han Chinese population.
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
authors.forename: J
authors.initials: J
authors.lastname: He
authors.affiliation: Division of Prevention and Population Science, National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Jaquish
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Division of Biostatistics, Washington University in St Louis School of Medicine, St Louis, MO, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Gu
authors.affiliation: Department of Epidemiology, University of Texas School of Public Health, Houston, TX, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Hixson
authors.affiliation: Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: D
authors.initials: D
authors.lastname: Gu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D002681:China; D004039:Diet, Sodium-Restricted; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000178:diet therapy / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C498898:SLC4A4 protein, human; D017673:Sodium Chloride, Dietary; D027982:Sodium-Bicarbonate Symporters