RESUMEN
The aim of the study was to assess whether selected genetic variants are associated with elite athlete performance in a group of 413 elite athletes and 451 sedentary controls. Polymorphisms in ACE, ACTN3, AGT, NRF-2, PGC1A, PPARG, and TFAM implicated in physical performance traits were analyzed. Additionally, polymorphisms in CHRNB3 and FAAH coding for proteins modulating activity of brain's emotion centers were included. The results of univariate analyses indicated that the elite athletic performance is associated with four polymorphisms: ACE (rs4341, P = 0.0095), NRF-2 (rs12594956, P = 0.011), TFAM (rs2306604, P = 0.049), and FAAH (rs324420, P = 0.0041). The multivariate analysis adjusted for age and gender confirmed this association. The higher number of ACE D alleles (P = 0.0021) and the presence of NRF-2 rs12594956 A allele (P = 0.0067) are positive predictors, whereas TFAM rs2306604 GG genotype (P = 0.031) and FAAH rs324420 AA genotype (P = 0.0084) negatively affect the elite athletic performance. The CHRNB3 variant (rs4950, G allele) is significantly more frequent in the endurance athletes compared with the power ones (P = 0.025). Multivariate analysis demonstrated that the presence of rs4950 G allele contributes to endurance performance (P = 0.0047). Our results suggest that genetic inheritance of psychological traits should be taken into consideration while trying to decipher a genetic profile of top athletic performance.
Asunto(s)
Atletas , Rendimiento Atlético , Polimorfismo Genético , Adulto , Alelos , Amidohidrolasas/genética , Proteínas de Unión al ADN/genética , Femenino , Genotipo , Humanos , Masculino , Proteínas Mitocondriales/genética , Factor 2 Relacionado con NF-E2/genética , Peptidil-Dipeptidasa A/genética , Polonia , Receptores Nicotínicos/genética , Deportes , Factores de Transcripción/genética , Adulto JovenRESUMEN
There is mounting evidence that genetic factors located in mitochondrial and nuclear genomes influence sport performance. Certain mitochondrial haplogroups and polymorphisms were associated with the status of elite athlete, especially in endurance performance. The aim of our study was to assess whether selected mitochondrial DNA (mtDNA) and nuclear DNA variants are associated with elite athlete performance in a group of 395 elite Polish athletes (213 endurance athletes and 182 power athletes) and 413 sedentary controls. Our major finding was that the mtDNA haplogroup H and HV cluster influence endurance performance at the Olympic/World Class level of performance (P = 0.018 and P = 0.0185, respectively). We showed that two polymorphisms located in the mtDNA control region were associated with achieving the elite performance level either in the total athlete's group as compared with controls (m.16362C, 3.8% vs 9.2%, respectively, P = 0.0025, odds ratio = 0.39, 95% confidence interval: 0.21-0.72), or in the endurance athletes as compared with controls (m.16080G, 2.35% vs 0%, respectively, P = 0.004). Our results indicate that mtDNA variability affects the endurance capacity rather than the power one. We also propose that mtDNA haplogroups and subhaplogroups, as well as individual mtDNA polymorphisms favoring endurance performance, could be population-specific, reflecting complex cross-talk between nuclear and mitochondrial genomes.
Asunto(s)
Rendimiento Atlético , ADN Mitocondrial/genética , Fuerza Muscular/genética , Resistencia Física/genética , Polimorfismo de Nucleótido Simple , Población Blanca/genética , Estudios de Casos y Controles , Núcleo Celular , Proteínas de Unión al ADN/genética , Femenino , Haplotipos , Humanos , Masculino , Proteínas Mitocondriales/genética , Músculo Esquelético/fisiología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Polonia , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: The relationship between different paraoxonase (PON) gene polymorphisms and the risk of Alzheimer's disease (AD) was studied several times and the results were controversial. METHODS: We investigated the association of 4 single-nucleotide polymorphisms (SNPs) of the PON1 (M55L; Q192R; -161C/T) and the PON2 (C311S) genes that were shown to affect the risk of sporadic AD. We studied 360 Caucasian cases with late-onset AD and 354 nondemented controls. RESULTS: No significant differences were observed between the studied PON SNPs and AD risk. The results did not change after stratification of the apolipoprotein E status. Meta-analyses of studies in Caucasians assessing the associations between the PON1 M55L, -161C/T and Q192R SNPs and the risk of AD were performed, and no associations were found. CONCLUSION: Our results suggest that the studied PON1 and PON2 polymorphisms are not associated with late-onset AD.
Asunto(s)
Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Arildialquilfosfatasa/genética , Polimorfismo Genético/genética , Factores de Edad , Edad de Inicio , Anciano , Alelos , Apolipoproteínas E/genética , ADN/genética , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Polonia/epidemiología , Polimorfismo de Nucleótido Simple , Población , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Regresión , Factores de Riesgo , Factores SexualesRESUMEN
Interleukin-1 is a potent proinflammatory cytokine involved in the pathophysiology of Alzheimer's disease (AD). We genotyped IL-1beta (-511 C/T) and the apolipoprotein E (APOE) common polymorphisms in a large case-controlled study in a Polish population. We included 332 patients with late-onset AD and 220 controls without any neurological deficit, cognitive complaints and history of neurological diseases, aged > or = 65 years. The distribution of the IL-1beta (-511 C/T) genotypes was similar to that in the controls (AD: C/C = 45.8%, C/T = 44.6%, T/T = 9.6% vs. controls: C/C = 53.9%, C/T = 38.3%, T/T = 7.3%, p > 0.05). Our study confirms previous reports that APOE epsilon4 is strongly related to the risk of AD (odds ratio = 6.60, 95% confidence interval 4.19-10.41). APOE status did not affect the distribution of the studied IL-1beta polymorphism. The IL-1beta (-511 C/T) polymorphism is not a risk factor for late-onset AD in a Polish population.
Asunto(s)
Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Interleucina-1beta/genética , Polimorfismo Genético , Edad de Inicio , Anciano , Anciano de 80 o más Años , Apolipoproteína E4/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Genotipo , Humanos , Masculino , Polonia/epidemiología , Factores de RiesgoRESUMEN
A 32-year-old woman diagnosed with very rapidly progressing early-onset Alzheimer's disease (EOAD), age of onset 29 years, and S170F mutation in presenilin 1 gene (PSEN1) is presented. Neuroimaging conducted 2 years after the first symptoms was typical for the advanced stage of Alzheimer's disease (AD), showing cortical brain atrophy, particularly within hippocampus, frontal and temporal cortex. The unaffected parents of the proband are not carriers of the mutation. The paternity was confirmed by microsatellite typing, strongly suggesting de novo origin of S170F mutation. In silico modeling of S170F mutation impact on presenilin 1 (PS1) transmembrane structure indicates that the mutation considerably alters putative interactions of PS1 with other proteins within gamma-secretase complex.
Asunto(s)
Enfermedad de Alzheimer/genética , Mutación , Presenilina-1/genética , Adulto , Enfermedad de Alzheimer/diagnóstico , Encéfalo/patología , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Modelos Moleculares , Fenilalanina , Serina , Factores de TiempoRESUMEN
The -22c/t polymorphism in the promoter of the presenilin 1 gene is associated with increased risk for Alzheimer's disease (AD) in some populations. It was shown that -22c allele is connected with two-fold decrease in promoter activity. We studied the impact of the polymorphism in groups of Polish late-onset and early-onset AD patients. Our results suggest that -22c/t polymorphism is not connected with AD in Polish population. The -22t allele showed a high degree of linkage disequilibrium with -2797 insertion of 13 bp. An additional -2923g/t polymorphism is also not connected with -22c/t and is not a risk factor for AD.