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© Copyright 2004 The British Pharmacological Society

160P University of Newcastle
Winter Meeting December 2004

THR164ILEβ2-adrenoceptor variant: a predictor for heart transplantation?

K. Leineweber, 1P. Rohe, 2A. Zittermann, 3G. Tenderich, 3H-G. Jakob, 2R. Körfer3 & O-E. Brodde1. 1Departments of Pathophysiology and Nephrology, 2Clinic of Cardio-Thoracic Surgery, University of Essen School of Medicine, D-45147 Essen and 3Heart- and Diabetes Centre, Ruhr-University of Bochum, D-32545 Bad Oeynhausen, Germany.

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Leineweber K
Rohe P
Zittermann A
Tenderich G
Jakob HG
Körfer R
Brodde OE

The human β2-adrenoceptor (β2AR) is encoded by an intron-less gene with nine known loci that vary within the normal population. The most common single nucleotide polymorphisms are located in the amino terminus at position 16 and 27, where an arginine (Arg) is substituted by a glycine (Gly; allele frequency ~ 50%) and a glutamine (Gln) is substituted by a glutamic acid (Glu; allele frequency ~ 25-35%), respectively. Additionally, a rare variant has been found at position 164 where, only in the heterozygous state, a threonine (Thr) is substituted by an isoleucine (Ile; allele frequency ~ 2-4%) [1]. Recently, Liggett et al.[2] genotyped 259 patients with chronic heart failure due to ischaemic or dilated cardiomyopathy and found that the allele frequencies for the Arg16Gly, Gln27Glu and Thr164Ile polymorphisms of the β2AR did not differ from those assessed in 212 healthy controls. However, those patients (n = 10) carrying the Thr164Ile polymorphism exhibited much more rapid progression to transplantation or death. Accordingly, we hypothesized that the Thr164Ile β2AR polymorphism should be more abundant in a collective of heart transplanted patients (HTX, n = 307) in comparison to patients with coronary artery disease (CAD, n = 222) and stable heart failure under treatment or to healthy controls (n = 215).

Table 1

β2AR-haplotypes

Healthy controls
CAD patients
HTX patients
 
n  = 215
n  = 222
n  = 307
 
n %
n %
n %
Thr164Thr
210
97.7
219
98.6
299
97.4

Arg16Arg-Gln27Gln-

34
15.8
31
13.9
38
12.4
Arg16Arg-Gln27Glu-
1
0.5
10
4.5
1
0.3
Arg16Gly-Gln27Gln-
35
16.2
39
17.6
45
14.7
Arg16Gly-Gln27Glu-
71
33.0
58
26.1
87
28.3

Arg16Gly-Glu27Glu-

0
0
0
0
2
0.7

Gly16Gly-Gln27Gln-

6
2.8
14
6.3
12
3.9
Gly16Gly-Gln27Glu-
34
15.8
27
12.2
43
14.0

Gly16Gly-Glu27Glu-

29
13.5
40
18.0
71
23.1

Thr164Ile

5
2.3
3
1.4
8
2.6
Arg16Gly-Gln27Gln-
3
1.4
0
0
3
0.9
Gly16Gly-Gln27Gln-
2
0.9
2
0.9
1
0.3
Gly16Gly-Gln27Glu-
0
0
1
0.5
4
1.3

n  = number of subjects

According to our results the Thr164Ile β2AR polymorphism does not accumulate in a collective of HTX-patients. Therefore the Thr164Ile β2AR variant neither predicts nor accelerates the progression of heart failure to heart transplantation.

1. Leineweber K, et al.Naunyn-Schmiedeberg´s Arch Pharmacol 2004; 369 : 1.
2. Liggett et al. J Clin Invest 1998; 102: 1534.