title: Interactive Effect of the KCNJ11 Ile337Val Polymorphism and Cigarette Smoking on the Antihypertensive Response to Irbesartan in Chinese Hypertensive Patients.
abstract: OBJECTIVE
  This study was designed to detect the association of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene polymorphism with antihypertensive therapeutic response to irbesartan in a large-scale Chinese hypertensive population.
  
  
  METHODS
  A total of 1,099 patients with essential hypertension were enrolled to receive a daily dose of 150 mg irbesartan for 27 days. Pretreatment baseline blood pressure (BP) and posttreatment BP on the 28th day were measured. Plasma irbesartan concentrations were measured by high-performance liquid chromatography-fluorescence. The KCNJ11 I337V gene polymorphism was determined using high-throughput TaqMan technology.
  
  
  RESULTS
  The HapMap data in the Han Chinese population showed that the I337V was used as a representative for 4 common functional polymorphisms. Our results showed that the association of antihypertensive response to irbesartan and the KCNJ11 genetic variant in the total sample was not significant. However, in nonsmokers, relative to the GG genotype, subjects with the homozygous AA genotype had a significantly higher therapeutic response to irbesartan (adjusted beta ± SE: 4.7±1.9 mm Hg, P = 0.015). In smokers, the subjects with the homozygous AA genotype had a significantly lower therapeutic response to irbesartan (adjusted beta ± SE: -5.6±2.5 mm Hg, P = 0.026). A multivariate linear regression model confirmed that there was a significant interactive effect between the KCNJ11 gene and smoking on irbesartan treatment (interaction P = 0.001).
  
  
  CONCLUSIONS
  The interactive effect of smoking status and the KCNJ11 genotype may influence the antihypertensive effects of irbesartan, which indicates a consideration for future individualized antihypertensive drug treatment.
authors: School of Life Sciences, Anhui University, Hefei, China; Institute of Biomedicine, Anhui Medical University, Hefei, China; shanqunjiang2014@163.com.
authors: Shanqun
authors: S
authors: Jiang
authors: Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada;
authors: Scott Alan
authors: SA
authors: Venners
authors: Institute for Aging Research, HSL and Harvard Medical School, Boston, Massachusetts, USA; Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, Massachusetts, USA;
authors: Yi-Hsiang
authors: YH
authors: Hsu
authors: Department of Statistics, University of Virginia, Charlottesville, Virginia, USA;
authors: Justin
authors: J
authors: Weinstock
authors: Institute of Biomedicine, Anhui Medical University, Hefei, China;
authors: Binyan
authors: B
authors: Wang
authors: Institute of Biomedicine, Anhui Medical University, Hefei, China;
authors: Houxun
authors: H
authors: Xing
authors: Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA;
authors: Xiaobin
authors: X
authors: Wang
authors: Institute of Biomedicine, Anhui Medical University, Hefei, China; Division of Epidemiology and Biostatistics, University of Illinois at Chicago School of Public Health, Chicago, Illinois, USA.
authors: Xiping
authors: X
authors: Xu
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000097:blood / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000097:blood / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D001713:Biphenyl Compounds / Q000097:blood / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D002851:Chromatography, High Pressure Liquid; D000075222:Essential Hypertension; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D000077405:Irbesartan; D016018:Least-Squares Analysis; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000208:ethnology; D013777:Tetrazoles / Q000097:blood / Q000627:therapeutic use*; D016896:Treatment Outcome; D000099161:Kcnj11 Channel
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D000077405:Irbesartan; D024661:Potassium Channels, Inwardly Rectifying; D013777:Tetrazoles; D000099161:Kcnj11 Channel
keywords: KCNJ11 gene polymorphism; blood pressure; blood pressure response; essential hypertension; hypertension; irbesartan; smoking.