RESUMO
BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.
Assuntos
Feto/fisiologia , Ganho de Peso na Gestação/genética , Gravidez/genética , Feminino , Estudo de Associação Genômica Ampla , Ganho de Peso na Gestação/fisiologia , Humanos , Gravidez/fisiologia , Gravidez/estatística & dados numéricosRESUMO
OBJECTIVES: Previous studies have found associations between Parkinson's disease (PD) and polymorphisms located within both the alpha-synuclein gene (SNCA) promoter and other gene regions. Our aim was to study SNCA gene markers in a closely matched Norwegian PD population to examine the genetic relationship between different polymorphisms associated with the disease. METHODS: We genotyped seven single nucleotide polymorphisms (SNPs) located in the SNCA promoter and two SNPs in the 3' gene region and seven microsatellite markers located across the gene in a closely matched series of 236 PD patients and 236 controls. Linkage disequilibrium (LD) structure was examined, and association of single markers and gene haplotypes analyzed. RESULTS: Several markers located across the SNCA gene were associated with PD, including marker alleles associated with disease in previous studies (Rep1 263-bp allele, rs356165 and rs356219). CONCLUSION: LD between associated marker alleles located across the SNCA gene suggests that a single genetic effect might explain the previous reported association in the promoter and 3' regions.
Assuntos
Predisposição Genética para Doença/genética , Doença de Parkinson/genética , Polimorfismo Genético/genética , alfa-Sinucleína/genética , Regiões 3' não Traduzidas/genética , Idoso , Idoso de 80 Anos ou mais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Química Encefálica/genética , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Frequência do Gene/genética , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Repetições de Microssatélites/genética , Noruega/epidemiologia , Doença de Parkinson/epidemiologiaRESUMO
BACKGROUND: Mutations in the PTEN-induced kinase 1 (PINK1) gene have been identified in recessively inherited and sporadic early-onset parkinsonism (EOP). METHODS: A total of 131 Norwegian patients diagnosed with Parkinson's disease were included. Of them, 89 participants had EOP (onset < or = 50 years); the remaining had familial late-onset disease (mean age at onset 64 years). PINK1 analysis included sequencing and gene dose assessment. Mutations were examined in 350 controls. RESULTS: Heterozygous missense mutations in PINK1 were found in 3 of 131 patients; none of the patients carried homozygous or compound heterozygous mutations. One of these three patients had a father affected by Parkinson's disease, and he carried the mutation. Three new and seven known polymorphic variants were identified, although none seemed to be associated with disease risk. CONCLUSIONS: PINK1 mutations are rare in Norwegian patients with EOP and familial Parkinson's disease. However, the data suggest that some heterozygous mutations might increase the risk of developing Parkinson's disease.
Assuntos
Predisposição Genética para Doença , Mutação de Sentido Incorreto , Doença de Parkinson/genética , Proteínas Quinases/genética , Adulto , Idade de Início , Idoso , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Dosagem de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Fatores de RiscoRESUMO
Many photoinduced processes including photosynthesis and human vision happen in organic molecules and involve coupled femtosecond dynamics of nuclei and electrons. Organic molecules with heteroatoms often possess an important excited-state relaxation channel from an optically allowed ππ* to a dark nπ* state. The ππ*/nπ* internal conversion is difficult to investigate, as most spectroscopic methods are not exclusively sensitive to changes in the excited-state electronic structure. Here, we report achieving the required sensitivity by exploiting the element and site specificity of near-edge soft X-ray absorption spectroscopy. As a hole forms in the n orbital during ππ*/nπ* internal conversion, the absorption spectrum at the heteroatom K-edge exhibits an additional resonance. We demonstrate the concept using the nucleobase thymine at the oxygen K-edge, and unambiguously show that ππ*/nπ* internal conversion takes place within (60 ± 30) fs. High-level-coupled cluster calculations confirm the method's impressive electronic structure sensitivity for excited-state investigations.Many photo-induced processes such as photosynthesis occur in organic molecules, but their femtosecond excited-state dynamics are difficult to track. Here, the authors exploit the element and site selectivity of soft X-ray absorption to sensitively follow the ultrafast ππ*/nπ* electronic relaxation of hetero-organic molecules.