Blood pressure response to potassium supplementation is associated with genetic variation in endothelin 1 and interactions with E selectin in rural Chinese.
OBJECTIVE
Although beneficial effects of potassium intake on blood pressure (BP) are well established, little is known about genetic factors that underlie interindividual variability in BP response to dietary potassium. In a previous study, we reported the first evidence for significant heritabilities for BP response in a dietary intervention study in rural Chinese. In this report, we extend our genetic studies to examine associations with polymorphisms in genes in vascular endothelial pathways.


METHODS
We genotyped study participants for 23 single nucleotide polymorphisms (SNPs) in endothelin 1 (EDN1), nitric oxide synthase 3, and E selectin (SELE). We tested 17 of these SNPs for associations with BP response to potassium supplementation in 1843 participants. Association tests used population-based [generalized estimation equation (GEE)] and family-based (quantitative transmission disequilibrium test) methods, as well as tests for gene-by-gene (GxG) interaction (generalized multifactor dimensionalilty reduction and GEE).


RESULTS
Single SNP analysis identified significant associations for several SNPs in EDN1 with multiple measures of BP response to potassium supplementation. The cumulative effects of the minor EDN1 alleles that showed significant associations were to reduce measures of BP response by 0.5-0.9 mmHg. We found significant evidence for effects of GxG interactions between EDN1 and SELE, even in the absence of individual associations with SELE variants.


CONCLUSIONS
Our results implicate variability in EDN1 and SELE as genetic factors that influence BP response to potassium intake. Although such epidemiological studies do not allow direct determination of physiologic mechanisms, our findings of joint effects identify EDN1 and SELE as targets for functional studies to determine their interactions in BP response to potassium intake.
Montasser
May E
ME
Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Shimmin
Lawrence C
LC
Gu
Donfeng
D
Chen
Jing
J
Gu
Charles
C
Kelly
Tanika N
TN
Jaquish
Cashell E
CE
Rice
Treva
T
Rao
D C
DC
Cao
Jie
J
Chen
Jichun
J
Liu
De-Pei
DP
Whelton
Paul
P
He
Jiang
J
Hixson
James E
JE
D000328:Adult; D000483:Alleles; D044466:Asian People; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D002681:China; D019040:E-Selectin / Q000235:genetics; D019332:Endothelin-1 / Q000235:genetics*; D016021:Epidemiologic Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017419:Potassium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D012424:Rural Population / Q000706:statistics & numerical data*
D019040:E-Selectin; D019332:Endothelin-1; D017419:Potassium, Dietary; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III