A genome-wide association study identifies novel gene associations with facial skin wrinkling and mole count in Latin Americans.

BACKGROUND: Genome-wide association studies (GWASs) have identified genes influencing skin ageing and mole count in Europeans, but little is known about the relevance of these (or other genes) in non-Europeans. OBJECTIVES: To conduct a GWAS for facial skin ageing and mole count in adults < 40 years old, of mixed European, Native American and African ancestry, recruited in Latin America. METHODS: Skin ageing and mole count scores were obtained from facial photographs of over 6000 individuals. After quality control checks, three wrinkling traits and mole count were retained for genetic analyses. DNA samples were genotyped with Illumina's HumanOmniExpress chip. Association testing was performed on around 8 703 729 single-nucleotide polymorphisms (SNPs) across the autosomal genome. RESULTS: Genome-wide significant association was observed at four genome regions: two were associated with wrinkling (in 1p13·3 and 21q21·2), one with mole count (in 1q32·3) and one with both wrinkling and mole count (in 5p13·2). Associated SNPs in 5p13·2 and in 1p13·3 are intronic within SLC45A2 and VAV3, respectively, while SNPs in 1q32·3 are near the SLC30A1 gene, and those in 21q21·2 occur in a gene desert. Analyses of SNPs in IRF4 and MC1R are consistent with a role of these genes in skin ageing. CONCLUSIONS: We replicate the association of wrinkling with variants in SLC45A2, IRF4 and MC1R reported in Europeans. We identify VAV3 and SLC30A1 as two novel candidate genes impacting on wrinkling and mole count, respectively. We provide the first evidence that SLC45A2 influences mole count, in addition to variants in this gene affecting melanoma risk in Europeans.

Evolution of postural stability after subthalamic nucleus stimulation in Parkinson's disease: a combined clinical and posturometric study.

OBJECTIVES: The occurrence of postural and balance disorders is a frequent feature in advanced forms of Parkinson's disease (PD). However, the pathological substrate of these disturbances is poorly understood. METHODS: In the present work, we investigated the evolution of posturometric parameters [center of pressure (CoP) displacement and CoP area] and axial scores between the pre-operative period and 3 months post-operative in seven PD patients who underwent bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). RESULTS: After surgery, the patients leaned backwards much more regardless of the STN stimulation, suggesting that surgery could have a deleterious effect on postural adaptation. During the post-operative period, the improvement in axial and postural scores was similar under levodopatherapy and DBS. On the other hand, DBS of the STN significantly reduced the CoP displacement and the CoP area, whereas levodopatherapy tended only to reduce the CoP displacement and to increase the CoP area significantly. CONCLUSIONS: These data suggest that DBS of the STN and levodopa do not act on the same neurological systems involved in posture regulation. DBS of the STN could improve posture via a direct effect on the pedunculopontine nucleus, which is known to be involved in posture regulation.

Functional and metabolic early changes in calf muscle occurring during nutritional repletion in malnourished elderly patients.

BACKGROUND: Metabolic alterations in skeletal muscle associated with malnutrition and the potential reversibility of such alterations during refeeding are not fully understood. OBJECTIVE: We characterized early changes in muscle during refeeding in malnourished, hospitalized elderly subjects. DESIGN: Muscle function, metabolism, and mass were evaluated in 24 clinically stable patients (11 were malnourished) by using isokinetic plantar flexor torque measurements and nuclear magnetic resonance (NMR) imaging for medial gastrocnemius mass assessment and 31P and 13C NMR spectroscopy for inorganic phosphate (Pi), phosphocreatine, and glycogen quantitation. RESULTS: Malnourished subjects had lower muscle mass (P < 0.02) and tended to have lower strength than did control subjects. In malnourished subjects, muscle strength increased after refeeding (P < 0.01) whereas muscle mass was unchanged. The ratio of Pi to ATP was lower in malnourished than in control subjects (P < 0.001) and increased during refeeding (P < 0.01). The mean ratio of phosphocreatine to ATP was lower in malnourished than in control subjects (P < 0.01) and increased to control values after refeeding. Muscle glycogen showed a scattered distribution for malnourished subjects; the mean value did not differ significantly from that of control subjects, either at baseline or after refeeding. CONCLUSIONS: The lower ratio of phosphocreatine to ATP in malnourished subjects could have resulted from either lower total muscle creatine or reduced oxidative capacities. High or normal glycogen associated with a low Pi-to-ATP ratio in malnourished subjects suggested preferential use of lipid over carbohydrate for energy supply, which is known to reduce muscle performance. The data suggest that normalization of muscle metabolite content after refeeding improves muscle strength in malnourished subjects.