AMPD1 C34T 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.

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.

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.

AMP Deaminase 1 Gene Polymorphism and Heart Disease—A Genetic Association That Highlights New Treatment

Nucleotide metabolism and signalling is directly linked to myocardial function. Therefore analysis how diversity of genes coding nucleotide metabolism related proteins affects clinical progress of heart disease could provide valuable information for development of new treatments. Several studies identified that polymorphism of AMP deaminase 1 gene (AMPD1), in particular the common C34T variant of this gene was found to benefit patients with heart failure and ischemic heart disease. However, these findings were inconsistent in subsequent studies. This prompted our detailed analysis of heart transplant recipients that revealed diverse effect: improved early postoperative cardiac function associated with C34T mutation in donors, but worse 1-year survival. Our other studies on the metabolic impact of AMPD1 C34T mutation revealed decrease in AMPD activity, increased production of adenosine and de-inhibition of AMP regulated protein kinase. Thus, genetic, clinical and biochemical studies revealed that while long term attenuation of AMPD activity could be deleterious, transient inhibition of AMPD activity before acute cardiac injury is protective. We suggest therefore that pharmacological inhibition of AMP deaminase before transient ischemic event such as during ischemic heart disease or cardiac surgery could provide therapeutic benefit.

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.

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 AMPD1 C34T mutation is not associated with the status of Israeli athletes

The adenosine monophosphate deaminase (AMPD1) gene seems to be an important regulator of skeletal muscle energy metabolism during exercise. A nonsense C34T mutation in the AMPD1 gene results in a premature stop codon, thus stopping protein synthesis. The aim of this study was to determine the AMPD1 C34T mutation frequency distribution among 155 Israeli athletes (endurance athletes, n=74; sprinters, n=81) and 142 healthy controls. Genotyping of the AMPD1 C34T (rs5810761) mutation was performed using polymerase chain reaction (PCR). Results showed that the genotype subtype did not differ by gender in the athletes (P=0.18) or the controls (P=0.79). The AMPD1 C34T genotype distribution was in line with Hardy-Weinberg equilibrium within all groups (P>0.05). The genotype distribution and allele frequencies were similar in the groups of endurance athletes, sprinters, and controls (P=0.455). Similarly, no significant differences were observed between the subgroups of elite endurance athletes and national endurance athletes (P=0.78), or between elite and national sprinters (P=0.46). In conclusion, the AMPD1 C34T mutation is not associated with endurance athletes’ status, at least in the present group of Israeli athletes. This suggests that elite athletic status can be achieved despite a partial deficiency in AMPD1, as marked by the AMPD1 CT genotype.

Plasma concentrations of TNF‐α and its soluble receptors sTNFR1 and sTNFR2 in patients with coronary artery disease

Tumour necrosis factor alpha (TNF-alpha) is implicated in post-ischemic myocardial dysfunction. Two distinct TNF-alpha receptors are shed from cell membranes and circulate in plasma as soluble sTNFR1 and sTNFR2 proteins. The aim of the study was to establish factors associated with plasma concentrations of TNF-alpha and its receptors in patients with coronary artery disease (CAD). Since adenosine inhibits the expression of TNF-alpha, two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism, i.e. AMP deaminase-1 (AMPD1, C34T) and adenosine deaminase (ADA, G22A), were analyzed. Plasma concentrations of TNF-alpha, sTNFR1, and sTNFR2 were measured using ELISA in 167 patients with CAD. Common factors significantly associated with higher TNF-alpha, sTNFR1, and sTNFR2 were lower glomerular filtration rate (GFR), older age, higher BNP, lower blood haemoglobin, and the presence of asthma or chronic obstructive pulmonary disease (COPD). Higher TNF-alpha and sTNFR1 concentrations were also associated with the presence of heart failure (HF), lower ejection and shortening fraction, the presence of diabetes or metabolic syndrome, lower serum HDL cholesterol, and higher uric acid. In multivariate analysis the common independent predictors of higher TNF-alpha, sTNFR1, and sTNFR2 were lower GFR, lower HDL cholesterol, higher BNP, and the presence of asthma or COPD. There were no associations between AMPD1 C34T or ADA G22A genotypes and TNF-alpha or its receptors. In conclusion, the concentrations of TNF-alpha, sTNFR1, and sTNFR2 reflect the impairment of cardiac and renal function in patients with CAD. Metabolic syndrome and diabetes are associated with higher plasma concentrations of TNF-alpha and its receptors.

Genotype Distributions in Top-level Soccer Players: A Role forACE?

We determined the genotype and allelic frequency of several genetic polymorphisms (ACE I/D, GDF-8K153R [and also E164K, P198A and I225T] and AMPD1 C34T) that are candidates to influence sports performance in a group of 54 male professional soccer players. Their results were compared with those of elite endurance male athletes (52 runners) and 123 sedentary, healthy men (controls). We found statistical significance for the ACE ID (chi (2)((2))=8.176, P=0.017) and II genotypes (chi(2)((2))=16.137, P<0.001) with a higher and lower frequency of ID ( P=0.005) and II (P<0.001), respectively, in soccer players than in endurance runners. Statistical significance was also reached for AMPD1 (with a higher frequency of the CT genotype in soccer players than in runners [chi(2)((2))=7.538, P=0.006]) but not for GDF-8 K153R. Since the ACE II genotype is associated with improved potential for endurance performance but with decreased training gains in muscle mass and strength, these findings together with previous results support the notion that elite soccer players tend to have a power/strength oriented genotype.

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 C34T Mutation Selectively Affects AMP-Deaminase Activity in the Human Heart

Possession of the nonsense mutation in AMPD1 C34T gene has been linked to improved survival in patients with heart failure, possibly by promoting the formation of adenosine. This mutation is known to decrease the activity of AMP-deaminase in skeletal muscle. We have found that the AMPD1 mutation decreases the activity of AMP-deaminase in the heart without changing the activity of any other enzymes of adenine nucleotide metabolism. Protective mechanism of this mutation may be thus induced by local cardiac metabolic changes.

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.