A Common Variant of the AMPD1 Gene Predicts Improved Cardiovascular Survival inPatients With Coronary Artery Disease

gene predicts improved cardiovascular
AMPD1
A common variant of the
survival in patients with coronary artery disease
Jeffrey L. Anderson, Jessica Habashi, John F. Carlquist, Joseph B. Muhlestein,
Benjamin D. Horne, Tami L. Bair, Robert R. Pearson, and Noal Hart
J. Am. Coll. Cardiol. 2000;36;1248-1252
This information is current as of May 4, 2011
The online version of this article, along with updated information and services, is
located on the World Wide Web at:

http://content.onlinejacc.org/cgi/content/full/36/4/1248
by on May 4, 2011
content.onlinejacc.org
Downloaded from

---

Journal of the American College of Cardiology
Vol. 36, No. 4, 2000
© 2000 by the American College of Cardiology
ISSN 0735-1097/00/$20.00
Published by Elsevier Science Inc.
PII S0735-1097(00)00850-0
Coronary Artery Disease
A Common Variant of the
AMPD1 Gene Predicts Improved Cardiovascular
Survival in Patients With Coronary Artery Disease
Jeffrey L. Anderson, MD, FACC, Jessica Habashi, BS, John F. Carlquist, PHD,
Joseph B. Muhlestein, MD, FACC, Benjamin D. Horne, MPH, Tami L. Bair, BS,
Robert R. Pearson, BS, Noal Hart, BS
Salt Lake City, Utah
OBJECTIVE
We tested whether a common AMPD1 gene variant is associated with improved cardiovas-
cular (CV) survival in patients with coronary artery disease (CAD).
BACKGROUND
Reduced activity of adenosine monophosphate deaminase (AMPD) may increase production
of adenosine, a cardioprotective agent. A common, nonsense, point variant of the AMPD1
gene (C34T) results in enzymatic inactivity and has been associated with prolonged survival
in heart failure.
METHODS
Blood was collected from 367 patients undergoing coronary angiography. Genotyping was
done by polymerase chain reaction amplification and restriction enzyme digestion, resulting
in allele-specific fragments. Coronary artery disease was defined as
70% stenosis of
1
coronary artery. Patients were followed prospectively for up to 4.8 years. Survival statistics
compared hetero- ( / ) or homozygotic ( / ) carriers with noncarriers.
RESULTS
Patients were 66
10 years old; 79% were men; 22.6% were heterozygous and 1.9%
homozygous for the variant AMPD1( ) allele. During a mean of 3.5
1.0 years, 52 patients
(14.2%) died, 37 (10.1%) of CV causes. Cardiovascular mortality was 4.4% (4/90) in
AMPD1( ) allele carriers compared with 11.9% (33/277) in noncarriers (p
0.046). In
multiple variable regression analysis, only age (hazard ratio, 1.11/year, p
0.001) and
AMPD1( ) carriage (hazard ratio, 0.36, p
0.053) were independent predictors of CV
mortality.
CONCLUSIONS Carriage of a common variant of the AMPD1 gene was associated with improved CV survival
in patients with angiographically documented CAD. The dysfunctional AMPD1( ) allele
may lead to increased cardiac adenosine and increased cardioprotection during ischemic
events. Adenosine monophosphate deaminase-1 genotyping should be further explored in
CAD for prognostic, mechanistic and therapeutic insights. (J Am Coll Cardiol 2000;36:
1248 –52) © 2000 by the American College of Cardiology
The adenosine monophosphate deaminase-1 (AMPD1)
be associated with prolonged survival in heart failure (6,7).
gene encodes an isoform of AMP deaminase (AMPD1, also
We tested whether it also is more broadly associated with
called myoadenylate deaminase) that is active in muscular
improved cardiovascular (CV) survival in patients with
tissue (1). Adenosine monophosphate deaminase-1 occupies
coronary artery disease (CAD) at high risk for future
a central position in adenosine nucleotide catabolism, cata-
ischemic events.
lyzing the conversion of AMP to inosine monophosphate,
the rate-limiting step for entry into the purine nucleotide
METHODS
cycle. Adenosine monophosphate deaminase-1 deficiency is
believed to cause exercise-induced myalgias and early fatigue
Study objectives. We tested whether carriage of the com-
in skeletal muscle (1–3). A common polymorphism in axon
mon variant allele of the AMPD1 gene, (AMPD1[ ]) was
2 of AMPD1, present in about 25% of Caucasians, causes a
associated with a reduced risk of CV death in patients with
C to T transition at nucleotide 34 (C34T) (2,3). This
documented CAD. We also tested its association with
nonsense transition encodes for a truncated, inactive en-
all-cause mortality.
zyme. A reduced activity of AMPD1 may increase persis-
Study population. Study subjects came from a consecutive
tence of adenosine (3,4), a cardioprotective molecule (5).
series of clinically stable patients of any age and either
Recently, the C34T variant of AMPD1 has been reported to
gender who underwent coronary angiography, were shown
to have severe CAD, consented for a blood draw at the time
From the University of Utah, LDS Hospital, Salt Lake City, Utah. Supported, in
of angiography (for confidential blood bank studies ap-
part, by grants from the Deseret Foundation, Intermountain Health Care, Salt Lake
proved by the hospital’s institutional review board) and were
City, Utah.
followed until death or for
2.5 years from entry. Subjects
Manuscript received December 29, 1999; revised manuscript received April 3,
2000, accepted June 2, 2000.
were primarily residents of Utah, a population ethnically
by on May 4, 2011
content.onlinejacc.org
Downloaded from

---

JACC Vol. 36, No. 4, 2000
Anderson et al.
1249
October 2000:1248 –52
AMPD1 Polymorphism and Survival in CAD Patients
alized by electrophoresis through a 2% agarose gel contain-
Abbreviations and Acronyms
ing ethidium bromide.
AMISTAD
Acute Myocardial Infarction Study of
Statistical considerations. Comparisons of characteristics
Adenosine
of survivors and nonsurvivors used chi-square (categorical
AMPD
adenosine monophosphate deaminase
variables) or unpaired t testing (continuous variables). Al-
CAD
coronary artery disease
lelic and genotypic frequencies were determined from ob-
CV
cardiovascular
HR
hazard ratio
served counts. Comparisons between allelic or genotypic
MI
myocardial infarction
frequency distributions used chi-square analysis. Hetero-
( / ) or homozygotic ( / ) carriers were compared with
noncarriers (wild type genotype, [ / ]) using survival
primarily of Northern European descent and genetically
statistics. The univariate predictive value of AMPD1( )
similar to the general U.S. Caucasian population (8).
carriage for CV and total survival was tested using Kaplan-
Data collection. At the time of angiography, key demo-
Meier analysis and log-rank statistics. Cox logistic regres-
graphic characteristics were recorded on standard data
sion analysis (stepwise, backward logistic regression ap-
forms, including age, gender and history of recent or remote
proach) was then used to determine univariate and multiple
myocardial infarction (MI) (9). Determination of presence
variable hazard ratios (HR) and the multiple variable pre-
and severity of CAD was made by each patient’s attending
dictive value of AMPD1( ) carriage, conditioned on 10
cardiologist, who was unaware of AMPD1 genotypes, using
other major CAD risk factors: age, gender, smoking status,
a format modified after the Coronary Artery Surgery Study
diabetic status, history of hypertension, history of hyperlip-
protocol (9,10). Severe CAD was defined as the presence of
idemia, family history, renal failure, presentation and initial
1 coronary lesions of
70% diameter stenosis in
1 major
therapy (SPSS v 9.0, Chicago, Illinois). The critical value
coronary artery or its primary branch. Mild or absent CAD
for entering and excluding variables in the model was set at
cases were excluded from this study of secondary risk. Index
p
0.10.
angiography occurred between August 1994 and December
1997.
Assessment of patient outcomes. The study patient co-
RESULTS
hort was followed until death or December 1998 (mean,
Baseline patient characteristics. A total of 367 patients
3.5
1.0 years of follow-up, range 2.5 to 4.8 years). Each
with documented CAD was entered, and 52 patients
subject was interviewed through a telephone survey that
(14.2%) died during the mean of 3.5
1.0 year follow-up,
determined the subject’s medical history since the index
37 (10.1%) of CV causes. Selected patient characteristics at
hospitalization. Deaths were determined when possible
study entry are summarized in Table 1 by survival status.
from a family member. Deaths were verified and other
Patients averaged 66
10 years of age, and 79% were men.
deaths determined as of March 1999 by a search of a
Survivors were younger at baseline, had higher ejection
national Social Security database. Subjects unable to be
fractions and tended to be men and smokers more fre-
contacted by telephone but not listed as deceased by the
quently than nonsurvivors.
national database were considered to be alive. Follow-up
Adenosine monophosphate deaminase-1 genotypic dis-
using the database allowed for 100% assessment of survival
tributions are shown in Table 2 for all patients and for
within the cohort.
survivors, those dying of any cause and those dying of a CV
DNA extraction. Approximately 20 ml to 30 ml of blood
cause. Of entered patients, 22.6% were heterozygous and
was withdrawn by venipuncture at the time of coronary
1.9% homozygous for the AMPD1( ) allele. Thus, 24.5%
angiography, collected in ethylenediaminetetraacetic acid,
were carriers of the polymorphic allele. In bivariate corre-
refrigerated at 4°C and processed within 24 h. The leuko-
lation analyses, AMPD1( ) carriage was unassociated with
cyte buffy coat was separated by centrifugation, and genomic
any other baseline factor, including ejection fraction.
DNA was extracted using a standard phenol:chloroform
AMPD1 genotype and survival. At the end of follow-up,
method as previously described (11).
CV mortality was 4.4% (4/90) for AMPD1( ) allele carriers
DNA genotyping. To identify the AMPD1 C34T variant
compared with 11.9% (33/277) for noncarriers. Figure 1
genotypes, polymerase chain reaction amplification was
shows the time-to-event (Kaplan-Meier) CV survival plot
performed with the following primers, as previously pub-
as a function of AMPD1( ) allele carriage. A significant
lished (12):
difference in survival by AMPD1 genotype was observed
AMPD1 5 CAT ACA GCT GAA GAG ACA 3
(log-rank statistic, 4.0, p
0.046). The HR of death for
AMPD1( ) carriage was 0.36 (0.13 to 1.0).
AMPD2 5 AAC ACT GCT GAA AAA TAG 3
Adenosine monophosphate deaminase-1( ) carriage was
Amplification reactions were performed in 15 l volumes
not associated with a reduction in noncardiovascular deaths
containing the two primers. Genotyping was performed as
(5.5% in carriers, 3.6% in noncarriers). When all-cause
previously reported (13). The reaction products were visu-
mortality was considered (CV plus non-CV), the difference
by on May 4, 2011
content.onlinejacc.org
Downloaded from

---

1250
Anderson et al.
JACC Vol. 36, No. 4, 2000
AMPD1 Polymorphism and Survival in CAD Patients
October 2000:1248 –52
Table 1. Patient Characteristics at Baseline by Survival Status
Characteristic
All Patients
Survivors
Deaths
CV Deaths
P1
P2
Number
367
315
52
37
—
—
Age (yr) (X
SD)
66.1
10.1
65.1
9.9
72.0
8.9
73.6
7.0
0.000
0.000
Gender (% male)
79.0
79.7
75.0
67.6
0.44
0.07
Diabetes (%)
19.6
19.0
23.1
24.3
0.50
0.45
Smoker (%)
25.9
27.6
15.4
10.8
0.06
0.03
Fam Hx (%)
36.8
37.5
32.7
32.4
0.51
0.56
h/o HTN (%)
49.9
49.5
51.9
45.9
0.75
0.62
h/o HLip (%)
48.8
50.8
36.5
40.5
0.06
0.29
Chol (mg/dl)
183
47
184
47
177
49
178
47
0.34
0.49
(n Chol)
(359)
(308)
(51)
(37)
EF (%)
59.5
17.3
61.0
16.4
50.1
19.9
50.4
19.5
0.000
0.006
(n EF)
(273)
(237)
(36)
(25)
Allele carrier (%)
24.5
26.1
17.3
10.8
Death, last f/u (mo)
38.6
11.3
42.3
5.4
16.4
12.3
14.8
11.4
—
—
P1 compares patients dying from any cause with survivors. P2 compares patients dying from cardiovascular causes with others.
Allele
AMPD1( ) variant allele; Chol
cholesterol; CV
cardiovascular; EF
ejection fraction; Fam Hx
family history; f/u
follow-up; HLip
hyperlipidemia;
HTN
hypertension.
was not significant (10.0% in AMPD1[ ] carriers, 15.5% in
DISCUSSION
noncarriers; p
0.19).
In multiple variable Cox regression analysis, including 12
Study summary. We found that patients with angiographi-
clinical and laboratory variables (age, gender, smoking,
cally documented CAD who were carriers of a common
diabetes, hypertension, hyperlipidemia, family history, total
genetic variant of the AMPD1 gene demonstrated improved
cholesterol, renal failure, presenting diagnosis, therapy at
CV survival. The AMPD1 variant did not predict develop-
index hospitalization and AMPD1[ ] carriage), only age
ment of CAD; rather, the effect appeared to be in prolong-
(HR, 1.11/year, p
0.001) and AMPD1( ) carriage (HR,
ing survival when heart disease was already present. Aden-
0.36, confidence interval 0.13–1.02, Wald chi-square p
osine monophosphate deaminase-1 genotype was
0.053) were selected as independent predictors of CV
unassociated with other risk factors, and its predictive value
mortality (Table 3).
was undiminished in multiple variable analyses (HR
The incomplete database for ejection fraction dissuaded
0.36). We speculate that the dysfunctional AMPD1( )
us from doing a formal determination of the relative
allele may lead to increased net production of adenosine
predictive value of the polymorphism in high and low
locally (in cardiac muscle [7]) and/or systemically (skeletal
ejection fraction subgroups. However, the reduction in CV
muscle source [6]), affording increased levels of cardiopro-
mortality did appear to be prominent in those with low
tection during ischemic events. If these results are verified,
( 40%) ejection fractions (0/9 with, vs. 13/34 without an
AMPD1 genotyping may provide useful prognostic, mech-
AMPD1[ ] allele and documented low ejection fraction,
anistic and therapeutic insights into CAD progression and
died).
prognosis.
In contrast with its value for secondary risk prediction,
Previous work. Recently, Loh et al. (6) reported an im-
AMPD1 polymorphism was not useful for prediction of the
proved clinical outcome associated with AMPD1( ) allele
presence or absence of CAD at initial angiography in an
carriage in a group of 132 patients with advanced heart
expanded consecutive series that included subjects with
failure referred for cardiac transplant evaluation. The mu-
normal angiograms (not shown).
tant AMPD1 allele was associated with an extended time
Table 2. Genotypic Distributions and Allelic Frequencies of AMPD1 Gene Polymorphism Among Patients by Survival Status
Wild type
Heterozygote
Homozygote
WT
Variant
( / )
( / )
( / )
( )
( )
Group
n (%)
n (%)
n (%)
Allele
Allele
A. All patients/all deaths
Survivors
234 (74.3)
76 (24.1)
5 (1.6)
544 (86.3)
86 (13.7)
Deaths
43 (82.7)
7 (13.5)
2 (3.8)
93 (89.4)
11 (10.6)
Total
277 (75.5)
83 (22.6)
7 (1.9)
637 (86.8)
97 (13.2)
B. CV deaths/CV survivors
No CV death
244 (73.9)
79 (23.9)
7 (2.1)
567 (85.9)
93 (14.1)
CV Deaths
33 (89.2)
4 (10.8)
0 (0)
70 (94.6)
4 (5.4)
Total
277 (75.5)
83 (22.6)
7 (1.9)
637 (86.8)
97 (13.2)
For A, death by genotype contingency table gives p
0.15 (chi-square). For B, CV death by genotype gives p
0.11 (chi-square), p
0.063 (likelihood ratio) or p
0.038
(linear-by-linear association).
CV
cardiovascular; WT
wild type.
by on May 4, 2011
content.onlinejacc.org
Downloaded from

---

JACC Vol. 36, No. 4, 2000
Anderson et al.
1251
October 2000:1248 –52
AMPD1 Polymorphism and Survival in CAD Patients
energy phosphates, inhibit oxygen free radical formation
and neutrophil activation and accumulation, improve mi-
crovascular function and participate in myocardial ischemic
preconditioning in experimental models of occlusion/
reperfusion, improving cardiac perfusion and function.
Earlier human studies (16,17), promising in themselves,
have been followed by a larger (n
236 patients) controlled
study, the Acute Myocardial Infarction Study of Adenosine
(AMISTAD) (15). In AMISTAD, adenosine (70
g/kg/
min) infused for 3 h as an adjunct to thrombolytic therapy
reduced radionuclide infarct size by 33% (p
0.03). A
larger trial to assess clinical events was proposed.
The role of AMPD1 in cardiac muscle is less well studied
than in skeletal muscle although it has been reported to be
expressed (together with AMPD2) in mammalian heart
(18). To date, neither myocardial nor skeletal muscle
adenosine levels have been measured in disease states and by
AMPD1 genotype.
Whatever the precise mechanism of adenosine’s benefit,
Figure 1. Kaplan-Meier survival-time plot for cardiovascular death by
the AMPD1( ) allele may provide carriers with an endog-
AMPD1 genotype (wild type vs. variant heterozygote or homozygote).
enous source of increased myocardial adenosine, improving
There are four events (4.4%) among 90 patients carrying the mutant
outcomes in those with CAD at high risk for future
polymorphism and 33 events (11.9%) among noncarriers, a statistically
significant difference (log-rank statistic 4.0, p
0.046; Breslow statistic
ischemic events.
4.1, p
0.043). Solid line
AMPD1( ) variant carrier; dotted line
Study strengths and limitations. This study extends pre-
variant noncarrier.
vious work on clinical consequences of the AMPD1 poly-
from the first hospitalization for heart failure to evaluation
morphism (6) by including a larger and broader spectrum of
for transplantation, with an HR for transplant-free survival
patients and evaluating their clinical course entirely prospec-
of 4.6. Our study is the first to confirm and extend these
tively. Adenosine monophosphate deaminase-1 genotype
findings to patients with CAD who were not selected by
was unassociated with other risk factors, and its association
ejection fraction or heart failure and who were studied
with CV survival was independent of other tested risk
prospectively after angiographic diagnosis.
factors in multiple variable analysis. However, the study is
Mechanisms of benefit. Loh et al. (6) speculated that the
only moderate in size, and the number of clinical events is
mechanism of benefit could be related to enhanced produc-
relatively small, so that the confidence intervals for CV
tion of adenosine in skeletal muscle that could increase
survival extension associated with AMPD1( ) are broad.
circulating levels of adenosine, leading to cardioprotection.
Similarly, the database for determining the relative protec-
Feldman et al. (7) editorialized that the short circulating
tive effect of the variant as a function of ejection fraction is
half-life of adenosine argued for a primarily local (myocar-
limited. Also, the study did not directly assess potential
dial) increase in net adenosine and hypothesized that
mechanisms of apparent benefit. The similarity of genotypic
adenosine levels might be increased in cardiac muscle in
frequencies in our CAD group to that in the general
patients carrying the variant allele (7). Adenosine, released
population further supports our observation about the ab-
by myocytes during ischemic stress (13), has been studied
sence of an effect on the development of CAD. Thus, for
extensively for a cardioprotective role although this remains
future studies disease progression or prognosis may be a
to be completely defined (14,15). As reviewed by Mahaffey
better focus than disease development. In conclusion, our
et al. (15), adenosine has been reported to replenish high-
findings, although promising, should be verified and ex-
Table 3. Cox Multiple Variable Logistic Regression Model* for Cardiovascular Death
Factor
Wald
HR(Exp B)
Lower CI
Upper CI
p Value
AMPD( )
3.74
0.36
0.13
1.02
0.053
Age/yr
21.96
1.11
1.06
1.16
0.001
*Using Backward Stepwise Conditional Logistic Regression method (SPSS v 9.0), entering age (year); male gender, h/o
hypertension, h/o hyperlipidemia, diabetes, family history, smoking, renal failure, adenosine monophosphate deaminase ( )
allele carriage ( /
or
/ ), all yes/no; presentation (stable angina, unstable angina, myocardial infarction), therapy at index
hospitalization (medical, angioplasty, or surgery) and total cholesterol (mg/dl). Systolic blood pressure (mm Hg) and diastolic
blood pressure (mm Hg) were included in separate analyses (with less complete datasets) with similar results. There were 358
patients with complete datasets entered and 37 events. P to exclude variables stepwise was 0.10 (ejection fraction was not entered
because of the large resulting number of incomplete datasets; that is, n
265).
CI
95% confidence interval; Exp B
exponential B; HR
hazard ratio.
by on May 4, 2011
content.onlinejacc.org
Downloaded from

---

1252
Anderson et al.
JACC Vol. 36, No. 4, 2000
AMPD1 Polymorphism and Survival in CAD Patients
October 2000:1248 –52
tended in larger and longer-term studies. If validated, they
8. McClellan T, Jorde LB, Skolnick MH. Genetic distances between the
suggest that AMPD1 genotyping may provide useful prog-
Utah Mormons and related populations. Am J Hum Genet 1984;36:
836 –57.
nostic, mechanistic and therapeutic insights into survival in
9. Taylor GS, Muhlestein JB, Wagner GS, Bair TL, Li P, Anderson JL.
patients with CAD as well as those with congestive heart
Implementation of a computerized cardiovascular information system
failure.
in a private hospital setting. Am Heart J 1998;136:792– 803.
10. Coronary Artery Surgery Study Principal Investigators and Their
Associates. Myocardial infarction and mortality in the Coronary
Reprint requests and correspondence: Dr. Jeffrey L. Anderson,
Artery Surgery Study (CASS) randomized trial. N Engl J Med
University of Utah School of Medicine (4A154), Department of
1984;310:750 – 4.
Medicine/Division of Cardiology, 50 North Medical Drive, Salt
11. Anderson JL, King GJ, Thomson MJ, et al. A mutation in the
Lake City, Utah 84132.
methylenetetrahydrofolate reductase gene is not associated with in-
creased risk for coronary artery disease or myocardial infarction. J Am
Coll Cardiol 1997;30:1206 –11.
REFERENCES
12. Gross M. New method for detection of C34-T mutation in the
AMPD1 gene causing myoadenylate deaminase deficiency. Ann
1. Sabina RL, Holmes EW. Myoadenylate deaminase deficiency. In:
Rheum Dis 1994;53:353– 4.
Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic
13. Dobson JG, Jr. Adenosine and adrenergic mediated effect in the heart.
and Molecular Bases of Inherited Disease. New York: McGraw-Hill,
In: Abdl-Elfattah ASA, Wechesler AS, editors. Purines and Myocar-
1995:1769 – 80.
dial Protection. Norwell, Mass: Kluwer Academic Publishers, 1995:
2. Morisaki T, Gross M, Morisaki H, Pongtratz G, Zollner N, Holmes
359 –71.
EW. Molecular basis of AMP deaminase deficiency in skeletal muscle.
14. Hori M, Kitakaze M. Adenosine, the heart, and coronary circulation.
Proc Natl Acad Sci USA 1992;89:6457– 61.
Hypertension 1991;18:565–74.
3. Sinkeler SPT, Joosten EMG, Wevers RA, et al. Myoadenylate
15. Mahaffey KW, Puma JA, Barbagelata A, et al., for the AMISTAD
deaminase deficiency: a clinical, genetic, and biochemical study in nine
Investigators. Adenosine as an adjunct to thrombolytic therapy for
families. Muscle Nerve 1988;11:312–7.
acute myocardial infarction. Results of a multicenter, randomized,
4. Sabina RL, Swain JL, Olanow CW, et al. Myoadenylate deaminase
placebo-controlled trial: the Acute Myocardial Infarction Study of
deficiency: functional and metabolic abnormalities associated with
Adenosine (AMISTAD) Trial. J Am Coll Cardiol 1999;34:1711–20.
disruption of the purine nucleotide cycle. J Clin Invest 1984;73:720 –
16. Garratt KN, Holmes DR, Molina-Viamonte V, et al. Intravenous
30.
adenosine and lidocaine in patients with acute myocardial infarction.
5. Leesar MA, Stoddard M, Ahmed M, Broadbent J, Bolli R. Precon-
ditioning of human myocardium with adenosine during coronary
Am Heart J 1998;136:196 –204.
angioplasty. Circulation 1997;95:2500 –7.
17. Leesar M, Stoddard M, Ahmed M, et al. Preconditioning of human
6. Loh E, Rebbeck TR, Mahoney PD, DeNofrio D, Swain JL, Holmes
myocardium with adenosine during coronary angioplasty. Circulation
EW. A common variant in AMPD1 gene predicts improved clinical
1997;95:2500 –7.
outcome in patients with heart failure. Circulation 1999;99:1422–5.
18. Morisaki T, Sabina RL, Holmes EW. Adenylate deaminase. A
7. Feldman AM, Wagner DR, McNamara DM. AMPD1 gene mutation
multigene family in humans and rats. J Biol Chem 1990;265:
in congestive heart failure. Circulation 1999;99:1397–9.
11482– 6.
by on May 4, 2011
content.onlinejacc.org
Downloaded from

---

gene predicts improved cardiovascular
AMPD1
A common variant of the
survival in patients with coronary artery disease
Jeffrey L. Anderson, Jessica Habashi, John F. Carlquist, Joseph B. Muhlestein,
Benjamin D. Horne, Tami L. Bair, Robert R. Pearson, and Noal Hart
J. Am. Coll. Cardiol. 2000;36;1248-1252
This information is current as of May 4, 2011
Updated Information
including high-resolution figures, can be found at:
& Services

http://content.onlinejacc.org/cgi/content/full/36/4/1248
References
This article cites 15 articles, 9 of which you can access for free
at:

http://content.onlinejacc.org/cgi/content/full/36/4/1248#BIBL

Citations
This article has been cited by 4 HighWire-hosted articles:
http://content.onlinejacc.org/cgi/content/full/36/4/1248#otherarti
cles
Rights & Permissions
Information about reproducing this article in parts (figures,
tables) or in its entirety can be found online at:
http://content.onlinejacc.org/misc/permissions.dtl
Reprints
Information about ordering reprints can be found online:
http://content.onlinejacc.org/misc/reprints.dtl
by on May 4, 2011
content.onlinejacc.org
Downloaded from

---