ACTN-3 and ACE genotypes in elite male Italian athletes

The ACE I/D and the ACTN-3 R577X polymorphisms are the most studied genes associated with elite athlete status, even if this association has been often conflicting. The aim of the present study was to investigate the association between the ACE and the ACTN3 genotypes and elite performance in Italian male athletes. The ACTN-3 R577X and the ACE I/D genotype distributions of 59 elite male Italian athletes practicing gymnastics (G; n = 17), 100 m-400 m running (R; n = 12), and playing soccer (S; n= 30) were compared with controls from Italian (C; n = 31) populations. For ACE distribution, athletes did not differ from controls (G, X2 = 0.37, df = 2, p = 0.82; R, X2 = 1.90, df = 2, p = 0.45; S, X2 = 1.48, df = 2, p = 0.47) and the DD genotype was at very high frequency in all groups (G = 53%, R= 50%, S = 60%, C = 45%). For ACTN-3 distribution, elite gymnasts showed a significant difference from controls (X2 = 6.57, df = 2, p = 0.03), showing an absence of XX genotype. Soccer players and runners did not differ from controls in ACTN-3 genotype distribution (R, X2 =0.43, df = 2, p = 0.80; S, X 2 = 1.25, df = 2, p = 0.53). Even if the ACE DD genotype is often positively associated with elite sprint/power athlete status, its high frequency in Italian populations eliminates the possibility of its exclusive association in Italian athletes. The results of ACTN3 genotypes suggest that RR genotype of ACTN-3 gene is a determinant of elite gymnasts status but it is not the key factor for achieving a top-level performance in soccer or track events

Investigation of Genetic Variants Associated with Tryptophan Metabolite Levels via Serotonin and Kynurenine Pathways in Patients with Bipolar Disorder

The kynurenine pathway (KP) may play a role in the pathophysiology of bipolar disorder (BD). We conducted a genome-wide association study (GWAS) to identify genetic variants associated with the plasma levels of the metabolites of tryptophan (TRP) via the serotonin (5-HT) and kynurenine (KYN) pathways in 44 patients with BD and 45 healthy controls. We assessed whether variants that were differentially associated with metabolite levels based on the diagnostic status improved the prediction accuracy of BD using penalized regression approaches. We identified several genetic variants that were significantly associated with metabolites (5-HT, 5-hydroxytryptophan (5-HTP), TRP, and quinolinic acid (QA) or metabolite ratios (5-HTP/TRP and KYN/TRP) and for which the diagnostic status exerted a significant effect. The inclusion of genetic variants led to increased accuracy in the prediction of the BD diagnostic status. Specifically, we obtained an accuracy of 0.77 using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The predictors retained as informative in this model included body mass index (BMI), the levels of TRP, QA, and 5-HT, the 5-HTP/TRP ratio, and genetic variants associated with the levels of QA (rs6827515, rs715692, rs425094, rs4645874, and rs77048355) and TRP (rs292212) or the 5-HTP/TRP ratio (rs7902231). In conclusion, our study identified statistically significant associations between metabolites of TRP via the 5-HT and KYN pathways and genetic variants at the genome-wide level. The discriminative performance of penalized regression models incorporating clinical, genetic, and metabolic predictors warrants a follow-up analysis of this panel of determinants

Melatonin MT1 receptors as a target for the psychopharmacology of bipolar disorder: a translational study

The treatment of bipolar disorder (BD) still remains a challenge. Melatonin (MLT), acting through its two receptors MT1 and MT2, plays a key role in regulating circadian rhythms which are dysfunctional in BD. Using a translational approach, we examined the implication and potential of MT1 receptors in the pathophysiology and psychopharmacology of BD. We employed a murine model of the manic phase of BD (Clock mutant (ClockΔ19) mice) to study the activation of MT1 receptors by UCM871, a selective partial agonist, in behavioral pharmacology tests and in-vivo electrophysiology. We then performed a high-resolution Nuclear Magnetic Resonance study on isolated membranes to characterize the molecular mechanism of interaction of UCM871. Finally, in a cohort of BD patients, we investigated the link between clinical measures of BD and genetic variants located in the MT1 receptor and CLOCK genes. We demonstrated that: 1) UCM871 can revert behavioral and electrophysiological abnormalities of ClockΔ19 mice; 2) UCM871 promotes the activation state of MT1 receptors; 3) there is a significant association between the number of severe manic episodes and MLT levels, depending on the genetic configuration of the MT1 rs2165666 variant. Overall, this work lends support to the potentiality of MT1 receptors as target for the treatment of BD

Sampling strategies in a linguistic isolate: results from mtDNA analysis

Objectives: Sampling strategies are crucial issues in population genetics and anthropological studies. The sampling choice is related to the research question and the type of markers used. In this research, we compared two different sampling strategies in the Sardinian linguistic isolate of Carloforte (Italy). Methods: A first sampling (N = 49) was carried out through grandparents criterion: individuals selected for the study were born and resident in Carloforte, and unrelated for at least three generations. A second sampling (N = 50) was based on founders surnames (FS): selected participants were proved to be descendants of the village founders, and to have no ancestors in common, at least up to the grandparental generation. Results: The group selected through FS showed a greater gene diversity, which was confirmed by both network and haplogroup analysis. Among the shared haplogroups, we find clear differences in their frequencies. Sampling through grandparents criterion showed essentially the same haplogroups found in Sardinia, and with similar frequencies. Interesting results came from genetic tree. The FS sampling clustered with Northern African populations and it is located very far from Italian and Sardinian populations, whereas the grandparents criterion sampling clustered with Italian populations and it is located close to the other Sardinian populations. Conclusions: Results showed that different sampling strategies can lead to contrasting results. As sampling through grandparents criterion is influenced by recent gene flow, we hypothesize that the difference observed with the two sampling strategies is due to the merging of Carloforte with Sardinian populations

Genetic markers and explosive leg-muscle strength in elite Italian soccer players

Aim. The aim of the present paper was to investigate the relationships between polymorphisms in ACTN3, ACE and BDKRB2 genes, soccer performance, and explosive leg-muscle strength in Italian soccer players. Methods. We examined 42 top-level Italian soccer players (S) and 106 sedentary healthly Italians, as a control group (C). Χ 2 test was used to look for the difference in genotype distribution of ACTN3, ACE and BDKRB2 between groups. The data were evaluated by forward stepwise multiple regression analysis with the Squat Jump (SJ) and Counter Movement Jump (CMJ) as dependent variables, as well as competition level (CL), ACTN-3, ACE and BDKRB2 genotypes as independent variables. Results. No significant difference was found between groups for ACE, ACTN-3 and BDKRB2 genotype distributions. Forward stepwise multiple regression analysis suggests a significant relationship between a) SJ νs. CL, ACE, and ACTN-3 and b) CMJ νs. CL. For SJ, the multivariate model combining genotypic data and competition level significantly predicted explosive leg-muscle strength in soccer players and variance explained by the function was 23.92%. Conclusion. An interaction of two polymorphisms (ACE and ACTN-3) might be able to discriminate quantitative traits crucial for the elite soccer performance, however the contribution of genetic factors to soccer performance is not so high

Hepatic angiosarcomatous transformation of a mediastinal germinal cell tumor: A care case report

Rationale: Mediastinal nonseminomatous germ cell tumor (NSGCT) is an uncommon entity. Metastatic hepatic sarcomatous transformation is rare. Patient concerns: We report a 24-year-old man with no previous related medical history presented with chest pain and left arm numbness. Diagnoses: The X-ray showed an anterior mediastinal mass. The chest computed tomography (CT) confirmed the presence of a mildly enhancing mass in the same location, without invasion of any vascular structure. A CT-guided biopsy was performed, revealing a primary mediastinal nonseminomatous germ cell tumor (NSGCT), yolk sac histology, with areas of somatic transformation to malignant nerve sheath tumor. After surgery patient was followed-up with imaging. Two years later a CT scan showed a new hepatic hyper vascular lesion, confirmed by a subsequent magnetic resonance imaging (MRI) and positron emission tomography (PET) scan. A CT-guided biopsy revealed a hepatic metastatic transformation to angiosarcoma of the primitive NSGCT. Interventions: The patient went on to received palliative chemotherapy. Outcomes: The patient is being followed-up regularly at the outpatient department. Lessons: Because of the potential of metastatic sarcoma arising from germ cell tumors, these patients should undergo periodical follow-up, with periodical scans. PET\CT scan might have a role in the follow-up of these patients