Influence of CYP2D6 and β2-adrenergic receptor gene polymorphisms on the hemodynamic response to propranolol in Chinese Han patients with cirrhosis.
OBJECTIVE
Propranolol is widely used to prevent gastroesophageal variceal bleeding; however, some patients could not benefit from propranolol. This study is to evaluate the relationship between CYP2D6 and β2-adrenergic receptor (β2-AR) gene polymorphisms and the hemodynamic response to propranolol in Chinese Han patients.


METHODS
The clinical data of patients with gastroesophageal varices undergoing hepatic venous pressure gradient (HVPG) measurement before and 7 days after oral propranolol administration in our department were collected. Four single nucleotide polymorphisms of CYP2D6 and β2-AR genes were detected. The relationship was identified by logistic regression model.


RESULTS
Thirty patients were involved in the analysis. Sixty milligram propranolol twice each day was well tolerated by all the patients. The initial and secondary average of HVPG was 17.4 ± 5.8 mmHg vs. 13.2 ± 4.8 mmHg, respectively (t = 5.726, P < 0.001). Twenty patients responded to propranolol. The mean reduction value of HVPG was 6.6 ± 3.6 mmHg (range from 3 to 19). Genotype analysis showed: 20 homozygotes for C/C188 and 10 for heterozygous C/T188, 8 homozygotes for G/G4268 and 22 heterozygotes for G/C4268, 14 homozygotes for Gly16 and 10 heterozygotes, and 6 homozygotes for Arg16, 27 homozygotes for Gln27 and 3 heterozygotes. The multivariate logistic regression analysis indicated that CYP2D6 (188C>T) genotype was an independent predicting factor for HVPG response to propranolol (P = 0.033).


CONCLUSIONS
CYP2D6 (188C>T) gene polymorphisms influence the hemodynamic response to propranolol in this population of Chinese Han patients with gastroesophageal varices. However, HVPG response cannot be completely predicted from CYP2D6 and β2-AR gene polymorphisms.
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Feng
F
Zhang
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Xuhong
X
Duan
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Ming
M
Zhang
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Zhenlei
Z
Li
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Qibin
Q
He
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Yi
Y
Wang
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Chengcheng
C
Miao
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Wenqi
W
Zhong
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Xiaoping
X
Zou
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Yuzheng
Y
Zhuge
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D044466:Asian People / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004932:Esophageal and Gastric Varices / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D056726:Genetic Association Studies; D006439:Hemodynamics; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2; D011433:Propranolol; D019389:Cytochrome P-450 CYP2D6
CYP2D6; HVPG response; liver cirrhosis; propranolol; β2-AR