C34T Polymorphism Research Articles

AMPD1 C34T Polymorphism (rs17602729) Is Not Associated with Post-Exercise Changes of Body Weight, Body Composition, and Biochemical Parameters in Caucasian Females.

Background: The C34T polymorphism (rs 17602729) in adenosine monophosphate deaminase 1 gene (AMPD1) is associated with muscular energy metabolism in exercise. However, the role of its potential modifying impact on exercise-induced changes in obesity related parameters is unknown. The aim of the study was to determine if the C34T polymorphism influences the effects of an exercise training. Methods: This study examines a group of one hundred and sixty-eight, young, non-obese Caucasian women in Poland who took part in a 12-week aerobic training program to determine the impact of allele and genotype distribution on training outcomes. Results: A two-way analysis of variance ANOVA was conducted assuming a dominant model by pooling rare homozygotes and heterozygotes (TT + CT, n = 79) and comparing against common homozygotes (CC, n = 89). Our results showed that the AMPD1 C34T polymorphism was not related with selected parameters in study group. After completing the 12-week training program, a wide array of parameters (body mass, body mass index, fat mass, free fat mass, total body water) were significantly changed in the study participants with the exception of AMPD1 genotypes, among whom no significant changes were observed. Conclusions: The results did not confirm that harboring the rs 17602729 T allele influences the effects of the training program.

P2Y12 Polymorphisms and the Risk of Adverse Clinical Events in Patients Treated with Clopidogrel: A Meta-Analysis.

Some studies have reported an association between P2Y12 gene polymorphisms and clopidogrel adverse outcomes with inconsistent results. We aimed to explore the relationship between P2Y12 polymorphisms and the risk of adverse clinical events in patients treated with clopidogrel through a meta-analysis. A systematic search of PubMed, Web of Science and the Cochrane Library was conducted. Retrieved articles were comprehensively reviewed and eligible studies were included, and the relevant data was extracted for this meta-analysis. All statistical tests were performed by the Review Manager 5.3 software. A total of 14 studies involving 8,698 patients were included. In the Han Chinese population, ischemic events were associated with P2Y12 T744C polymorphism in the CC vs TT+CT genetic model (OR=3.32, 95%CI=1.62-6.82, P=0.001), and the events were associated with P2Y12 C34T polymorphism in the TT+TC vs CC genetic model (OR=1.70, 95%CI=1.22-2.36, P=0.002). However, ischemic events were not related to P2Y12 G52T polymorphism (TT+TG vs GG: OR=1.13, 95%CI=0.76-1.68, P=0.56; TT vs GG+TG: OR=2.02, 95%CI=0.65-6.28, P=0.22). The associations between the P2Y12 polymorphism and ischemic events were not significant in T744C, G52T and C34T genotype for another subgroup of the Caucasian population (P>0.05). Only two studies referring to bleeding events were included in this analysis of C34T polymorphism, and no significant association was found (TT+TC vs CC: OR=1.07, 95%CI=0.37-3.15, P=0.90). In the Caucasian population, P2Y12 gene polymorphisms are not associated with clinical events. However, in the Chinese Han population, P2Y12 T744C and C34T polymorphisms are significantly associated with adverse clinical events.

Effects of AMPD1 gene C34T polymorphism on cardiac index, blood pressure and prognosis in patients with cardiovascular diseases: a meta-analysis

BackgroundThe meta-analysis was aimed to evaluate the effects of AMPD1 gene C34T polymorphism on cardiac function indexes, blood pressure and prognosis in patients with cardiovascular diseases (CVD).MethodsEligible studies were retrieved through a comprehensive search of electronic databases and manual search. Then the high-quality studies met the rigorous inclusion and exclusion criteria, as well as related to the subject was selected for the study. Comprehensive data analyses were conducted using STATA software 12.0.ResultsThe study results revealed that CVD patients with CT + TT genotype of AMPD1 C34T polymorphism presented elevated left ventricular ejection fraction (LVEF) (%) and reduced left ventricular end diastolic dimension (LVEDD) (mm) as compared with CC genotype, moreover, the subgroup analysis found that the LVEF (%) was markedly higher in heart failure (HF) patients carrying CT + TT genotype than CC genotype. Besides, the systolic blood pressure (SBP) (mmHg) in CVD patients with CT + TT genotype was obviously decreased in contrast with the CC genotype. Patients suffered from HF with different genotypes (CT + TT and CC) of AMPD1 C34T polymorphism exhibited no significant differences in total survival rate and cardiac survival rate.ConclusionsOur current meta-analysis indicated that the T allele of AMPD1 gene C34T polymorphism may be correlated with LVEF, LVEDD and SBP, which plays a protective role in the cardiac functions and blood pressure in CVD patients, but had no effects on total survival rate and cardiac survival rate for HF.

Genotyping, Platelet Activation, and Cardiovascular Outcome in Patients after Percutaneous Coronary Intervention: Two Pieces of the Puzzle of Clopidogrel Resistance

Objectives: Individual platelet responses to antiplatelet therapy depend on genetic, cellular, and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet responses to antiplatelet treatment. We aimed to evaluate the impact of CYP2C19 and C34T P2Y12 genotyping on platelet reactivity and cardiovascular outcome in patients after percutaneous coronary intervention (PCI) on clopidogrel treatment. Methods: We enrolled 408 patients with stable coronary artery disease (CAD) receiving aspirin and clopidogrel (75 mg/day) 1 month after PCI. High on-treatment platelet reactivity was evaluated using the VerifyNow Assay in a subset of patients. CYP2C19*2 and C34T P2Y12 genotyping was performed by real-time polymerase chain reaction. The primary end point was the composite of death or hospitalization for cardiovascular causes, and patients were followed for a median time of 13 months. Results: In the total study population, 37% were carriers of at least 1 CYP2C19*2 loss-of-function allele, and 53% were carriers of at least 1 C34T loss-of-function allele. Interestingly, homozygotes of the CYP2C19*2 loss-of-function allele had significantly increased P2Y12 reaction units (PRU) (p = 0.007). However, PRU did not differ between carriers and noncarriers of the C34T loss-of-function allele (p = 0.41). Moreover, carriers of CYP2C19*2 had an increased hazard ratio (HR) for the occurrence of the primary end point (for carriers HR = 1.96, 95% CI 1.05-3.66, p = 0.03), whereas the C34T polymorphism had no impact on the cardiovascular outcome (p = 0.17). Finally, PRU was associated with cardiovascular outcome even after adjustment for the presence of any reduced function allele polymorphism. Conclusions: We documented a different effect of CYP2C19 and P2Y12 receptor polymorphisms on platelet reactivity and cardiovascular outcome in CAD patients after PCI on clopidogrel treatment. Importantly, increased platelet reactivity adversely affects the cardiovascular outcome independently of the studied polymorphisms.

P2Y12 receptor gene polymorphism and the risk of resistance to clopidogrel: A meta-analysis and review of the literature

A number of investigators have evaluated the association between T744C, G52T and C34T polymorphisms in the P2Y12 receptor gene and clopidogrel resistance (CR), but the results of their research are controversial. To quantify the evidence addressing this issue, we performed a meta-analysis of all available studies to evaluate the above association between the 3 different P2Y12 genotypes and CR in patients suffering from cardiovascular diseases. This study included articles up to October 2015. We performed a systematic search of PubMed, Embase, Web of Science, Cochrane database, China National Knowledge Infrastructure (CNKI) and WanFang database. Articles meeting the inclusion criteria were included and accumulated by meta-analysis including 5769 participants from 15 individual studies. For G52T polymorphism, a significant relationship between the P2Y12 receptor gene and CR was found under the dominant genetic model (p < 0.05). There was a clear positive correlation between the C34T polymorphism and CR under the dominant, recessive, additive genetic models, respectively (p < 0.05). The evidence from the present metaanalysis indicates that P2Y12 receptor gene C34T and G52T polymorphism might be a risk factor for the poor response to the platelet in patients on clopidogrel therapy, whereas a lack of association was found for T744C polymorphism examined by various genetic models.

The influence of genetic polymorphisms on performance and cardiac and hemodynamic parameters among Brazilian soccer players.

This study investigated whether ACTN3 R577X, AMPD1 C34T, I/D ACE, and M235T AGT polymorphisms can affect performance tests such as jumping, sprinting, and endurance in 220 young male athletes from professional minor league soccer team from São Paulo Futebol Clube, Brazil. I/D ACE and M235T AGT polymorphisms were also analyzed according to cardiac and hemodynamic parameters. Athletes were grouped or not by age. DNA from saliva and Taqman assays were used for genotyping 220 athletes and the results were associated with performance tests. Ventricle mass, ventricle end-diastolic diameter, end-diastolic volume, and ejection fraction were assessed by echocardiogram. Arterial pressure, heart rate, and oximetry were assessed by a cardioscope. The main results of this study were that athletes who carried RR/RX (ACTN3) and DD (ACE) genotypes presented better performance during jump and sprint tests. On the other hand, athletes with ID/II genotype presented better results during endurance test, while AGT genotypes did not seem to favor the athletes during the evaluated physical tests. CC genotype (AMPD1) only favored the athletes during 10-m sprint test. Although there are environmental interactions influencing performance, the present results suggest that RR/RX ACTN3 and ACE DD genotypes may benefit athletes in activities that require strength and speed, while II ACE genotype may benefit athletes in endurance activities. This information could help coaches to plan the training session to improve the athletes' performance.

Association between the C34T polymorphism of the AMPD1 gene and essential hypertension in Malaysian patients.

The aim of this study was to determine whether C34T, a common polymorphism of the adenosine monophosphate deaminase 1 gene (AMPD1), is associated with essential hypertension (EH). We hypothesize that C34T is associated with the development of EH. A case-control design was used for this study. The DNA was extracted using a commercial kit from the whole blood of 200 patients with hypertension and 200 subjects without hypertension from selected Malaysian ethnicities (Malays, Chinese, and Indians). Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis were used for genotyping. The C34T gene polymorphism of AMPD1 was significantly associated with EH in the Malaysian subjects (P < 0.0001). The genotype frequencies of CC, CT, and TT were 6%, 79%, and 15%, respectively, among hypertensive subjects, while no TT genotypes were observed in the normotensive subjects. Further, the frequency of hypertension was higher among T allele carriers than C carriers (OD = 9.94; 95%CI = 6.851-14.434). There were significant differences in the systolic blood pressure, diastolic blood pressure, and pulse pressure (P ˂ 0.05) between the normotensive and hypertensive Malaysian subjects; we believe those difference were caused by the C34T polymorphism. For the first time in Malaysia, the current study provides evidence that a common polymorphism of the AMPD1 gene (C34T) is strongly associated with EH.

Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population.

The aim of the present study was to establish the gene frequency of six polymorphisms of the ABCB1, CYP3A5, CYP2C19, and P2RY12 genes in a population resident of Mexico City. The proteins encoded by these genes have been associated with the absorption, and biotransformation of clopidogrel. The ABCB1 T3435C, CYP3A5 V3 A6986G, P2RY12 G52T, P2RY12 C34T, CYP2C19 V2 and V3 (positions G681A and G636A, respectively), polymorphisms were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 269 healthy unrelated Mexican Mestizo individuals. The CYP2C19 V3 G636A polymorphism was not detected in the Mexican Mestizos population. However, the studied population presented significant differences (P < 0.05) in the distribution of the T3435C, A6986G, G681A, G52T and C34T polymorphisms when compared to reported frequencies of Amerindian of South America, Caucasian, Asian, and African populations. In summary, the distribution of the ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms distinguishes to the Mexican Mestizos population from other ethnic groups.

AMPD1 rs17602729 is associated with physical performance of sprint and power in elite Lithuanian athletes.

BackgroundThe C34T genetic polymorphism (rs17602729) in the AMPD1 gene, encoding the skeletal muscle-specific isoform of adenosine monophosphate deaminase (AMPD1), is a common polymorphism among Caucasians that can impair exercise capacity. The aim of the present study was twofold: (1) to determine the C34T AMPD1 allele/genotype frequency distributions in Lithuanian athletes (n = 204, stratified into three groups: endurance, sprint/power and mixed) and compare them with the allele/genotype frequency distributions in randomly selected healthy Lithuanian non-athletes (n = 260) and (2) to compare common anthropometric measurements and physical performance phenotypes between the three groups of athletes depending on their AMPD1 genotype.ResultsThe results of our study indicate that the frequency of the AMPD1 TT genotype was 2.4% in the control group, while it was absent in the athlete group. There were significantly more sprint/power-orientated athletes with the CC genotype (86.3%) compared with the endurance-orientated athletes (72.9%), mixed athletes (67.1%), and controls (74.2%). We determined that the AMPD1 C34T polymorphism is not associated with aerobic muscle performance phenotype (VO2max). For CC genotype the short-term explosive muscle power value (based on Vertical Jump test) of athletes from the sprint/power group was significantly higher than that of the endurance group athletes (P < 0.05). The AMPD1 CC genotype is associated with anaerobic performance (Vertical Jump).ConclusionsThe AMPD1 C allele may help athletes to attain elite status in sprint/power-oriented sports, and the T allele is a factor unfavourable for athletics in sprint/power-oriented sports categories. Hence, the AMPD1 C allele can be regarded as a marker associated with the physical performance of sprint and power. Replications studies are required to confirm this association.

Effects of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and clinical outcome in patients with acute coronary syndromes undergoing stent-based coronary intervention

Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients. Methods In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months. Results Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 (group 4). Group 4 had the lowest ADP-inhibition (49.74±32.61) and the highest prevalence of clopidogrel low response (29.7%) of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 (8.5%) than in the other three groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 (3.7%) were not significantly different than that of group 1 (1.5%). Conclusion Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Is the C34T Polymorphism of the AMPD1 Gene Associated with Athlete Performance in Rowing?

The skeletal muscle-specific isoform of adenosine monophosphate deaminase (AMPD) is one of the most important regulators of muscle energy metabolism. A nonsense C to T transition in nucleotide 34 (C34T) in exon 2 of AMPD1 gene converts the codon CAA into the premature stop-codon TAA. 127 Polish male rowers including Olympic and world champions were recruited for this study. Controls samples were obtained from 251 unrelated volunteers. Statistically significant differences in genotype distribution were observed when only a whole group of rowers (88.19% CC, 11.81% CT, 0% TT; p=0.009) were compared with controls (75.31% CC, 23.10% CT, 1,59% TT). A significant deficiency of the T allele compared to control samples was noted in the elite rowers (4.55%, p=0.021) and non-elite rowers (6.63%, p=0.023), whereas this trend was even stronger when compared with the controls for the whole group of rowers (5.91%, p=0.002). Our results suggest that the T allele is associated with physical performance level, therefore, it may be included in the group of performance altering polymorphisms as a negative factor to athletic performance.

Distribution of the AMPD1 C34T polymorphism in Polish power-oriented athletes

The aims of this study were to determine the distribution of the AMPD1 genotype among groups of high-level Polish power-oriented athletes, and to investigate potential associations between genetic polymorphism in exon 2 of the AMPD1 gene and power-oriented athlete status. Altogether, 158 male Polish power-oriented athletes were genotyped by PCR-RFLP. The genetic control group comprised 160 unrelated male volunteers. We observed significant differences in genotype distribution when all 158 athletes (89.25% CC, 10.75% CT, 0.00% TT; P = 0.0025) were compared with controls (75.00% CC, 23.75% CT, 1.25% TT). A significant deficiency of the T allele was noted in all subgroups (short-distance runners: 5.21%, P = 0.032; short-distance swimmers: 5.56%, P = 0.031; weightlifters: 5.36%, P = 0.024) compared with controls (13.13%), while this trend was even stronger when the frequency of the T allele was compared between controls and all 158 athletes (5.38%, P = 0.0007). Our results indicate a lower frequency of the AMPD1 exon 2 T34 allele in elite Polish power-oriented athletes. Our data suggest that the C allele may help athletes to attain elite status in power-oriented sports.

The Impact of the AMPD1 Gene Polymorphism on Exercise Capacity in Patients with Chronic Heart Failure

Background: Previous studies have shown that the adenosine monophosphate deaminase 1(AMPD1)C34T polymorphism is associated with a longer transplant free survival in patients with congestive heart failure. It has been postulated that increased regional and circulating adenosine may contribute to vasodilatation and after-load reduction. However, this polymorphism is also associated with a skeletal myopathy. It is unclear whether this polymorphism has beneficial impact, through enhanced endogenous after load reduction, or detrimental impact, through impaired skeletal muscle metabolism, on the exercise capacity of patients with heart failure.

Association of C34T AMPD1 gene polymorphism with features of metabolic syndrome in patients with coronary artery disease or heart failure

Objective. The common C34T polymorphism in the AMP deaminase‐1 (AMPD1) gene results in an inactive enzyme in homozygotes for the mutated T allele. Some studies have shown an association of T allele with longer survival in heart failure (HF) and/or coronary artery disease (CAD). The aim of this study was to assess genotype–phenotype correlations in such patients, with emphasis on components of the metabolic syndrome. Methods. Ninety‐seven patients with CAD without HF (CAD+ HF–) and 104 with HF (HF+) were genotyped by PCR‐RFLP. The genetic control group comprised 200 newborns. Results. No significant differences were found in the frequency of AMPD1 genotypes between the groups. In the CAD+ HF– group, the carriers of T allele compared to CC homozygotes had significantly lower values of waist circumference (89.5±8.5 versus 97.7±11.2 cm; p = 0.00029), waist/hip ratio (p = 0.0059) and BMI (p = 0.045). There was no diabetes or fasting glycaemia ⩾126 mg/dL in T carriers, while these features were present in 25 % of CC homozygotes (p = 0.0024). In the HF+ group, a tendency towards a lower prevalence of diabetes (20 % versus 41 %; p = 0.068) and significantly lower systolic blood pressure (p = 0.048) were observed in T allele carriers. Conclusions. C34T AMPD1 polymorphism may be associated with reduced frequency of obesity in CAD patients and of hyperglycaemia and diabetes in both CAD and HF patients. Morphometric parameters associated with adipose tissue distribution and parameters of glucose metabolism should be analysed as potential confounders in further studies on the role of polymorphisms of AMPD1 and other genes associated with AMP and adenosine metabolism in cardiovascular disease.

A novel mutation found in a study of sprint exercise performance in AMP deaminase deficiency

We here report a novel mutation found in subjects that lacked AMPD activity and were heterozygote for the C34T in the AMPD1 gene. AMP deaminase (AMPD) deficiency is an inherited disorder of skeletal muscle found in approximately 2% of Caucasian population. The deficiency is connected with an altered ATP catabolism and a loss of increase in plasma ammonia in response to high intensity exercise. In most cases the deficiency is due to a C34T transition in the AMPD1-gene. In a study with 139 healthy, physically active subjects of both genders, 12 AMPD-deficient subjects were studied. Although, 3 of the subjects were not homozygote for the C34T polymorphism. Sequencing and allele-specific PCR amplification assays were used to identify the mutation and a single nucleotide deletion in exon 5, 404delT was found. The frameshift mutation results in a premature termination of translation at codon 175. Three of the deficient subjects were compound heterozygote carrying the common C34T and the 404delT mutation. A 30-s Wingate test was used to assess muscle power, muscle endurance, and fatigability. The healthy AMPD-deficient subjects performed an approximately 10% lower mean power.

The Genotype Combination of the P2Y12 Gene Might Confer Greater Risk for Coronary Artery Disease.

BACKGROUND: The adenosine diphosphate (ADP) receptor P2Y12 plays a central role in platelet function, and this receptor is therapeutic target for thrombotic disorders. Previously, the P2Y12 gene was reported to have genetic polymorphisms, H1H2 haplotype (C139T, T744C, insertion 801A, and G52T) and C34T. The effect of these polymorphisms on the risk for arterial thrombosis, however, remains controversial. In this study, we screened the sequence variations in the P2Y12 gene, and performed case-control study to investigate the association between P2Y12 polymorphisms and coronary artery disease (CAD).METHODS AND RESULTS: Written informed consent was obtained from all study subjects who were Japanese males. Screening of polymorphisms in the P2Y12 gene comprising exon1, exon2, and intron1 was analyzed in 20 control subjects. As a result, new haplotypes were defined: haplotype A: 145C, 139C, 744T, and 1210T, haplotype B: 145T, 139T, 744C, insertion 801A, and 1210C. The G52T and C34T polymorphism were not linked with this haplotype. We next analyzed the relationship between these P2Y12 polymorphisms and susceptibility of CAD in a case-control study. One hundred and two patients with CAD were recruited at Keio University Hospital with a diagnosis of myocardial infarction or angina pectoris. CAD patients whose coronary lesions were confirmed by coronary angiography (identified stenosis ≥50%) were eligible for this study. To match CAD patients for sex and age at diagnosis of CAD, 257 healthy control subjects were recruited at their regular checkups. They had no clinical or laboratory evidence of past vascular disorders. Genotypes of the AB, C34T, and G52T polymorphisms were determined by single nucleotide primer extension-based method. We observed that the genotype frequencies of the AB (AA vs AB+BB), C34T (CC vs CT+TT), and G52T (GG vs GT+TT) did not differ between the CAD and control groups (p= 0.0635 for AB, p=0.2090 for C34T, and p=0.0816 for G52T). When study subjects were divided into the combination of two homozygous carriers (genotype combination), the AA and 34CC genotypes, and other genotypes (others), the frequency of genotype combination in CAD patients was significantly higher than that in controls (p=0.0058). Moreover, association of the genotype combination with the prevalence of CAD, adjusted for other risk factors (body mass index, smoking, hypertension, hyperlipidemia, and diabetes mellitus), was analyzed by a multiple logistic regression model, and adjusted odds ratio was 2.0 (95% CI, 1.1–3.5, p=0.0147) for the relation between CAD and the genotype combination.CONCLUSIONS: The combination of AA haplotype and 34CC genotype is highly associated with the risk of CAD. The present data point out the importance of genotypic combination, but not single specific polymorphism, to examine the association between CAD and P2Y12 polymorphisms.

The impact of the AMPD1 gene polymorphism on exercise capacity, other prognostic parameters, and survival in patients with stable congestive heart failure: A study in 686 consecutive patients

Previous studies have demonstrated that the adenosine monophosphate deaminase 1 (AMPD1) C34T polymorphism may be associated with survival in cardiac populations with a protective effect of the T allele. However, these studies included limited number of patients with few cardiovascular events. We prospectively analyzed the impact of the C34T polymorphism of the AMPD1 gene in 686 unrelated white patients with stable congestive heart failure related to left ventricular systolic dysfunction. Patients underwent echocardiography, radionuclide angiography, and a cardiopulmonary exercise test. Blood samples were drawn for standard and hormonal determinations and for genetic analysis. There were 517 (75%) CC homozygotes, 155 (23%) CT heterozygotes, and 14 (2%) TT mutated homozygotes. We did not demonstrate any impact of this polymorphism on clinical, biologic, echocardiographic, radionuclide, and exercise parameters in the whole population and in ischemic and nonischemic subgroups of patients. During a median follow-up period of 3 years, there were 145 cardiac-related deaths and 6 urgent transplantations. There was no impact of this polymorphism on survival. In our population, we did not demonstrate any effect of the C34T polymorphism of the AMPD1 gene on major congestive heart failure parameters and on survival.

Evaluation of AMPD1 C34T genotype as a predictor of mortality in heart failure and post–myocardial infarction patients

The AMPD1 gene C34T polymorphism has previously been associated with prolonged survival in small cohorts of heart failure (HF) and coronary artery disease patients. This study aimed to corroborate the association of the AMPD1 C34T polymorphism with survival in larger myocardial infarction (MI) and HF cohorts. Genotypes were obtained for 935 post-MI (PMI) and 433 patients with established HF, with median follow-up times of 5.4 and 3.1 years, respectively. At admission, cardiac function was assessed by nuclear ventriculography (PMI) and echocardiography (HF) and plasma cardiac neurohormones were assayed. Differences in mortality by AMPD1 genotype did not achieve significance, either for the overall HF (P = .07) or the overall PMI group (P = .28), but AMPD1 genotype predicted mortality in patients of both cohorts with a history of MI (HxMI). In contrast to previous studies, the mutant T allele was associated with poorer outcome. Mortality in HF HxMI patients was significantly different between genotype groups (n = 144, mortality CC 56.5%, CT/TT 77.8%, P = .027), but not in patients without HxMI. In PMI patients, the association of genotype with survival in the HxMI subgroup trended toward significance (n = 147, mortality CC 29.8%, CT/TT 45.5%, P = .093). Multivariate analysis of combined PMI and HF cohorts showed that HxMI patients with CT/TT genotype were at greater risk than all other groups (P < .001). This study suggests that AMPD1 C34T genotype is not a predictor of survival in heart disease patients, except possibly those with HxMI.

AMPD1 gene polymorphism and the vasodilatory response to ischemia

Peripheral vasculature resistance can play an important role in affecting blood pressure and the development of cardiovascular disease. A better understanding of the genes that encode vasodilators, such as adenosine, will provide insight into the mechanisms underlying cardiovascular disease. We tested whether the adenosine monophosphate deaminase-1 ( AMPD1) C34T gene polymorphism was associated with the vasodilatory response to ischemia in Caucasian females aged 18–35 years. Blood samples ( n = 58) were analyzed for the C34T variant and resulted in the following genotype groups: CC ( n = 45) and CT ( n = 13). Mean blood pressure (MBP), heart rate, and forearm blood flow (FBF) measured by venous occlusion plethysmography were measured at baseline and at 1 (peak FBF), 2 and 3 min of vasodilation during reactive hyperemia following 5 min of arm ischemia. To control for interindividual variability in baseline FBF and forearm vascular resistance (FVR) the percent change in FBF and FVR were calculated for each min. The percent decrease in FVR was significantly greater in the CT compared to the CC genotype group (− 40 ± 4% vs. − 24 ± 3%, P = 0.01) during the 2nd min of reactive hyperemia. The percent increase in FBF tended to be greater in the CT compared to the CC genotype group (+ 69 ± 9% vs. + 42 ± 9%, P = 0.07) during the 2nd min of reactive hyperemia after adjustment for percent body fat. Consistent with previous findings of increased production of adenosine during exercise in individuals carrying a T allele, our findings suggest that the AMPD1 C34T polymorphism is associated with vasodilatory response to ischemia in the peripheral vasculature because individuals with the T allele had a greater vasodilatory response to ischemia.

A common variant of the AMPD1 gene predicts improved survival in patients with ischemic left ventricular dysfunction

Background A recent retrospective study suggested that the adenosine monophosphate deaminase (AMPD)-1 gene variant C34T predicts outcome in heart failure patients. This variant might lead to ischemic preconditioning by increasing tissue adenosine. We tested whether the survival benefit of C34T occurs preferentially in the setting of ischemic left ventricular dysfunction. Methods and results A consecutive cohort of patients (n = 390) with left ventricular ejection fraction <40% was evaluated. In the ischemic patient subgroup (n = 210) multivariate analysis identified AMPD1 T allele carriage (hazard ratio = 0.43, confidence interval = 0.20–0.94, P = .035) as an independent predictor of transplant-free cardiovascular survival. No benefit was found in the nonischemic group although the number of events was too small to reliably exclude a benefit by genotype. Conclusion The AMPD1 C34T polymorphism influences transplant-free cardiovascular survival in the setting of ischemic left ventricular dysfunction.