BACKGROUND: This cross-sectional study investigated the relationship between genetic variations in monocarboxylate transporter genes and blood lactate production and removal after high-intensity efforts in humans. The study was conducted to explore how genetic variations in the MCT1, MCT2, and MCT4 genes influenced lactate dynamics and to advance the field of sports genetics by pinpointing critical genetic markers that can enhance athletic performance and recovery. METHODS: 337 male athletes from Poland and the Czech Republic underwent two intermittent all-out Wingate tests. Before the tests, DNA samples were taken from each participant, and SNP (single nucleotide polymorphism) analysis was carried out. Two intermittent all-out tests were implemented, and lactate concentrations were assessed before and after these tests. RESULTS: Sprinters more frequently exhibited the haplotype TAC in the MCT2 gene, which was associated with an increase in the difference between maximum lactate and final lactate concentration. Additionally, this haplotype was linked to higher maximum lactate concentration and was more frequently observed in sprinters. The genotypic interactions AG/T- and GGxT- (MCT1 rs3789592 x MCT4 rs11323780), TTxTT (MCT1 rs12028967 x MCT2 rs3763979), and MCT1 rs7556664 x MCT4 rs11323780 were all associated with an increase in the difference between maximum lactate concentration and final lactate concentration. Conversely, the AGxGG (MCT1 rs3789592 x MCT2 rs995343) interaction was linked to a decrease in this difference. The relationship between maximum lactate concentration and genotypic interactions can be observed as follows: when ATxTT (MCT2 rs3763980 x MCT4 rs11323780) or CTxCT (MCT1 rs10857983 x MCT2 rs3763979) genotypic combinations are present, it leads to a decrease in maximum lactate concentration. Similarly, the combination of CTxCT (MCT1 rs4301628 x MCT2 rs3763979), CT x TT (MCT1 rs4301628 x MCT4 rs11323780), and CTxTT (MCT1 rs4301628 x MCT2 rs3763979) results in decreased maximum lactate concentration. CONCLUSIONS: The TAC haplotype (rs3763980, rs995343, rs3763979) in the MCT2 gene is associated with altered lactate clearance in sprinters, potentially affecting performance and recovery by elevating post-exercise lactate concentrations. While MCT4 rs11323780 is also identified as a significant variant in lactate metabolism, suggesting its role as a biomarker for sprinting performance, further investigation is necessary to clarify underlying mechanisms and consider additional factors. Based on elite male athletes from Poland and the Czech Republic, the study may not generalize to all sprinters or diverse athletic populations. Although genetic variants show promise as biomarkers for sprinting success, athletic performance is influenced by a complex interplay of genetics, environment, and training extending beyond MCT genes.

• Klíčová slova
• Athletic training, Genetic predisposition, Genetic variants, Genotype, Haplotype, Lactate kinetics, Sprint,
• MeSH
• dospělí MeSH
• genotyp MeSH
• haplotypy * MeSH
• jednonukleotidový polymorfismus * MeSH
• kinetika MeSH
• kyselina mléčná * krev   metabolismus   MeSH
• lidé MeSH
• mladý dospělý MeSH
• přenašeče monokarboxylových kyselin * genetika   metabolismus   MeSH
• průřezové studie MeSH
• sportovci MeSH
• svalové proteiny * genetika   metabolismus   MeSH
• symportéry * genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kyselina mléčná * MeSH
• monocarboxylate transport protein 1 MeSH Prohlížeč
• přenašeče monokarboxylových kyselin * MeSH
• SLC16A2 protein, human MeSH Prohlížeč
• SLC16A4 protein, human MeSH Prohlížeč
• svalové proteiny * MeSH
• symportéry * MeSH

BACKGROUND: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency. METHODS: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1·5 years and between patients who were or were not underweight by age 1-3 years (defined as a bodyweight-for-age Z score <-2 SDs or <5th percentile according to WHO definition). Other objectives were to assess neurocognitive function and outcomes, and clinical parameters including anthropometric characteristics, biochemical markers, and neuroimaging findings. FINDINGS: Between Oct 14, 2014, and Jan 17, 2020, we enrolled 151 patients with 73 different MCT8 (SLC16A2) mutations. Median age at diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0). 32 (21%) of 151 patients died; the main causes of mortality in these patients were pulmonary infection (six [19%]) and sudden death (six [19%]). Median overall survival was 35·0 years (95% CI 8·3-61·7). Individuals who did not attain head control by age 1·5 years had an increased risk of death compared with patients who did attain head control (hazard ratio [HR] 3·46, 95% CI 1·76-8·34; log-rank test p=0·0041). Patients who were underweight during age 1-3 years had an increased risk for death compared with patients who were of normal bodyweight at this age (HR 4·71, 95% CI 1·26-17·58, p=0·021). The few motor and cognitive abilities of patients did not improve with age, as evidenced by the absence of significant correlations between biological age and scores on the Gross Motor Function Measure-88 and Bayley Scales of Infant Development III. Tri-iodothyronine concentrations were above the age-specific upper limit in 96 (95%) of 101 patients and free thyroxine concentrations were below the age-specific lower limit in 94 (89%) of 106 patients. 59 (71%) of 83 patients were underweight. 25 (53%) of 47 patients had elevated systolic blood pressure above the 90th percentile, 34 (76%) of 45 patients had premature atrial contractions, and 20 (31%) of 64 had resting tachycardia. The most consistent MRI finding was a global delay in myelination, which occurred in 13 (100%) of 13 patients. INTERPRETATION: Our description of characteristics of MCT8 deficiency in a large patient cohort reveals poor survival with a high prevalence of treatable underlying risk factors, and provides knowledge that might inform clinical management and future evaluation of therapies. FUNDING: Netherlands Organisation for Health Research and Development, and the Sherman Foundation.

• MeSH
• biologické markery analýza   MeSH
• dítě MeSH
• dospělí MeSH
• duševní poruchy etiologie   patologie   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezinárodní agentury MeSH
• míra přežití MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• následné studie MeSH
• nemoci svalů etiologie   patologie   MeSH
• neurovývojové poruchy etiologie   patologie   MeSH
• předškolní dítě MeSH
• přenašeče monokarboxylových kyselin nedostatek   genetika   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• symportéry nedostatek   genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• přenašeče monokarboxylových kyselin MeSH
• SLC16A2 protein, human MeSH Prohlížeč
• symportéry MeSH

We evaluate the mRNA expression of monocarboxylate transporters 1 and 4 (MCT1 and MCT4) in skeletal muscle (soleus, red and white gastrocnemius), heart and liver tissues in mice submitted to a single bout of swimming exercise at the maximal lactate steady state workload (MLSSw). After 72 h of MLSS test, the animals were submitted to a swimming exercise session for 25 min at individual MLSSw. Tissues and muscle samples were obtained at rest (control, n=5), immediately (n=5), 5 h (n=5) and 10 h (n=5) after exercise for determination of the MCT1 and MCT4 mRNA expression (RT-PCR). The MCT1 mRNA expression in liver increased after 10 h in relation to the control, immediate and 5 h groups, but the MCT4 remained unchanged. The MCT1 mRNA expression in heart increased by 31 % after 10 h when compared to immediate, but no differences were observed in relation to the control group. No significant differences were observed for red gastrocnemius in MCT1 and MCT4 mRNA expression. However, white gastrocnemius increased MCT1 mRNA expression immediately when compared to rest, 5 and 10 h test groups. In soleus muscle, the MCT1 mRNA expression increased immediately, 5 and 10 h after exercise when compared to the control. In relation to MCT4 mRNA expression, the soleus increased immediately and 10 h after acute exercise when compared to the control group. The soleus, liver and heart were the main tissues that showed improved the MCT1 mRNA expression, indicating its important role in controlling MLSS concentration in mice.

• MeSH
• anaerobní práh fyziologie   MeSH
• játra metabolismus   MeSH
• kondiční příprava zvířat metody   MeSH
• kosterní svaly fyziologie   MeSH
• mikro RNA metabolismus   MeSH
• myokard metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• orgánová specificita MeSH
• plavání fyziologie   MeSH
• přenašeče monokarboxylových kyselin genetika   metabolismus   MeSH
• symportéry genetika   metabolismus   MeSH
• tělesná námaha fyziologie   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mikro RNA MeSH
• monocarboxylate transport protein 1 MeSH Prohlížeč
• přenašeče monokarboxylových kyselin MeSH
• Slc16a7 protein, mouse MeSH Prohlížeč
• symportéry MeSH