Genome-wide linkage and positional candidate gene study of blood pressure response to dietary potassium intervention: the genetic epidemiology network of salt sensitivity study.
BACKGROUND
Genetic determinants of blood pressure (BP) response to potassium, or potassium sensitivity, are largely unknown. We conducted a genome-wide linkage scan and positional candidate gene analysis to identify genetic determinants of potassium sensitivity.


RESULTS
A total of 1906 Han Chinese participants took part in a 7-day high-sodium diet followed by a 7-day high-sodium plus potassium dietary intervention. BP measurements were obtained at baseline and after each intervention using a random-zero sphygmomanometer. Significant linkage signals (logarithm of odds [LOD] score, >3) for BP responses to potassium were detected at chromosomal regions 3q24-q26.1, 3q28, and 11q22.3-q24.3. Maximum multipoint LOD scores of 3.09 at 3q25.2 and 3.41 at 11q23.3 were observed for absolute diastolic BP (DBP) and mean arterial pressure (MAP) responses, respectively. Linkage peaks of 3.56 at 3q25.1 and 3.01 at 11q23.3 for percent DBP response and 3.22 at 3q25.2, 3.01 at 3q28, and 4.48 at 11q23.3 for percent MAP response also were identified. Angiotensin II receptor, type 1 (AGTR1), single-nucleotide polymorphism rs16860760 in the 3q24-q26.1 region was significantly associated with absolute and percent systolic BP responses to potassium (P=0.0008 and P=0.0006, respectively). Absolute (95% CI) systolic BP responses for genotypes C/C, C/T, and T/T were -3.71 (-4.02 to -3.40), -2.62 (-3.38 to -1.85), and 1.03 (-3.73 to 5.79) mm Hg, respectively, and percent responses (95% CI) were -3.07 (-3.33 to -2.80), -2.07 (-2.74 to -1.41), and 0.90 (-3.20 to 4.99), respectively. Similar trends were observed for DBP and MAP responses.


CONCLUSIONS
Genetic regions on chromosomes 3 and 11 may harbor important susceptibility loci for potassium sensitivity. Furthermore, the AGTR1 gene was a significant predictor of BP responses to potassium intake.
Kelly
Tanika N
TN
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Hixson
James E
JE
Rao
Dabeeru C
DC
Mei
Hao
H
Rice
Treva K
TK
Jaquish
Cashell E
CE
Shimmin
Lawrence C
LC
Schwander
Karen
K
Chen
Chung-Shuian
CS
Liu
Depei
D
Chen
Jichun
J
Bormans
Concetta
C
Shukla
Pramila
P
Farhana
Naveed
N
Stuart
Colin
C
Whelton
Paul K
PK
He
Jiang
J
Gu
Dongfeng
D
D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics*; D002681:China / Q000453:epidemiology; D002880:Chromosomes, Human, Pair 11; D002893:Chromosomes, Human, Pair 3; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017419:Potassium, Dietary / Q000494:pharmacology*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012982:Sodium, Dietary / Q000494:pharmacology; D055815:Young Adult
C544065:AGTR1 protein, human; D017419:Potassium, Dietary; D044140:Receptor, Angiotensin, Type 1; D012982:Sodium, Dietary