Genome-Wide Linkage and Positional Candidate Gene Study of Blood Pressure Response to Dietary Potassium Intervention

Abstract

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. Methods and 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. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00721721.