Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport

Merezhinskaya, Natalya; Fishbein, William N.; Davis, John I.; Foellmer, John W.

doi:10.1002/(sici)1097-4598(200001)23:1<90::aid-mus12>3.0.co;2-m

Cited by 103 publications

(104 citation statements)

References 31 publications

(40 reference statements)

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“…Genomic DNA from the subjects was analysed by polymerase chain reaction (PCR) amplification of a fragment containing the A1470T polymorphism of the MCT1 gene (rs 1049434, exon 5) and following direct sequencing. The primers used for amplification were as follows 10 : sense primer 5'-ACA CAT ACT GGG CAT GTG GC-3' (1455-1474); antisense primer 5'-AAA TCC CAT CAA TGA ACA ACT GGT ATG ATT TCC AC-3' (1807-1841). PCR reaction was made in a total volume of 50 (iL containing: 3 (xL genomic DNA, 1.5 mM MgC12,0.2 mM dNTP mix, 0.4 (xM primer, 4% dimethyl sulfoxide (SIGMA) and 1U Taq polymerase (BioTaq Polimerase, BioLine, London, UK).…”

Section: Methodsmentioning

confidence: 99%

“…An A1470T polymorphism (rs 1049434) in the MCTl gene (resulting in a glutamic acid to-aspartic acid change in codon 490), whose physiological role is still indeterminate, has been also reported. 10 Although there appear to be no clinical effects of this polymorphism, a 40% reduction of lactate transport rate has been identified in the erythrocytes of both individuals homozygous and heterozygous for this polymorphic variant. 10 In high-intensity exercise, anaerobic metabolism accounts for the subsequent lactic accumulation, 11 especially in resistance training, 12 ' 13 making it relevant to study this metabolite and its movement in the body during strength training.…”

Section: Introductionmentioning

confidence: 99%

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MCT1 genetic polymorphism influence in high intensity circuit training: A pilot study

Cupeiro

Benito

Maffulli

et al. 2010

Journal of Science and Medicine in Sport

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Monocarboxylate Transporter 1 (MCTl) mediates the transport of the main fraction of lactate across the sarcolemma. A common polymorphic MCTl variant has been identified, but its role in high intensity exercise performance has not been defined. We investigated the influence of MCTl A1470T polymorphism (rsl049434) on lactate accumulation after high intensity circuit training. Ten men aged 20-26 performed three controlled circuit training (CWT) sessions at 60%, 70%, and 80% of the 15 repetition maximum (15 RM), in non-consecutive days. CWT included three sets of a circuit of eight exercises, obtaining lactate measurements immediately after each set had been completed. Two independent variables were analysed: MTC1 genotypes according to the presence or absence of the A1470T polymorphism, and the intensity of circuit training. Genotype distributions were in Hardy-Weinberg equilibrium, being 30% wild-type, 50% heterozygotes, and 20% mutated homozygotes. Mean lactate concentration at 80% of 15RM were significantly higher than the mean lactate values at the other intensities (p < 0.01). Significant differences between genetic groups were found in the lactate accumulation slope at 80% of 15 RM (p = 0.02) and in the maximal lactate concentration reached by all subjects in the study (L max ) (p = 0.03). The carriers of the A1470T polymorphism in the MTC1 gene seem to exhibit a worse lactate transport capability into the less active muscle cells for oxidation.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MCT1 genetic polymorphism influence in high intensity circuit training: A pilot study

Cupeiro

Benito

Maffulli

et al. 2010

Journal of Science and Medicine in Sport

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“…The first condition associated with a lactate transporter defect that was later proposed to be caused by a mutation in the SLC16A1 gene, was reported as rare cryptic exercise intolerance or fatigue syndrome, manifested through muscle cramping and chest pain, caused by impaired lactate removal after intense exercise in otherwise healthy people 42. Whether the mutations or rather impaired interactions with the ancillary protein CD147/basigin are responsible for the MCT1 deficiency was questioned afterward since the in vitro experiments could not prove the reduced transporter activity of the mutated isoform compared with wildtype MCT1 15…”

Section: Mcts In Other Diseasesmentioning

confidence: 99%

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Fisel

Schaeffeler

Schwab

2018

Clinical Translational Sci

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The solute carrier (SLC) SLC16 gene family comprises 14 members and encodes for monocarboxylate transporters (MCTs), which mediate the absorption and distribution of monocarboxylic compounds across plasma membranes. As the knowledge about their physiological function, activity, and regulation increases, their involvement and contribution to cancer and other diseases become increasingly evident. Moreover, promising opportunities for therapeutic interventions by directly targeting their endogenous functions or by exploiting their ability to deliver drugs to specific organ sites emerge.

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“…In humans, several single nucleotide polymorphisms (SNPs) were found in MCTs proteins (Lean & Lee 2009, Merezhinskaya et al 2000, Cupeiro et al 2010. In horses, studies searching for polymorphisms were also conducted.…”

Section: Genetic Study Of Monocarboxylatesmentioning

confidence: 99%

Candidate genes for performance in horses, including monocarboxylate transporters

et al. 2017

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Some horse breeds are highly selected for athletic activities. The athletic potential of each animal can be measured by its performance in sports. High athletic performance depends on the animal capacity to produce energy through aerobic and anaerobic metabolic pathways, among other factors. Transmembrane proteins called monocarboxylate transporters, mainly the isoform 1 (MCT1) and its ancillary protein CD147, can help the organism to adapt to physiological stress caused by physical exercise, transporting lactate and H+ ions. Horse breeds are selected for different purposes so we might expect differences in the amount of those proteins and in the genotypic frequencies for genes that play a significant role in the performance of the animals. The study of MCT1 and CD147 gene polymorphisms, which can affect the formation of the proteins and transport of lactate and H+, can provide enough information to be used for selection of athletic horses increasingly resistant to intense exercise. Two other candidate genes, the PDK4 and DMRT3, have been associated with athletic potential and indicated as possible markers for performance in horses. The oxidation of fatty acids is highly effective in generating ATP and is controlled by the expression of PDK4 (pyruvate dehydrogenase kinase, isozyme 4) in skeletal muscle during and after exercise. The doublesex and mab-3 related transcription factor 3 (DMRT3) gene encodes an important transcription factor in the setting of spinal cord circuits controlling movement in vertebrates and may be associated with gait performance in horses. This review describes how the monocarboxylate transporters work during physical exercise in athletic horses and the influence of polymorphisms in candidate genes for athletic performance in horses.

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Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport

Cited by 103 publications

References 31 publications

MCT1 genetic polymorphism influence in high intensity circuit training: A pilot study

MCT1 genetic polymorphism influence in high intensity circuit training: A pilot study

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Candidate genes for performance in horses, including monocarboxylate transporters

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