Association of exceptional parental longevity and physical function in aging

Offspring of parents with exceptional longevity (OPEL), who are more likely to carry longevity-associated genotypes, may age more successfully than offspring of parents with usual survival (OPUS). Maintenance of physical function is a key attribute of successful aging. While many genetic and non-genetic factors interact to determine physical phenotype in aging, examination of the contribution of exceptional parental longevity to physical function in aging is limited. The LonGenity study recruited a relatively genetically homogenous cohort of Ashkenazi Jewish (AJ) adults age 65 and older, who were defined as either OPEL (having at least one parent who lived to age 95 or older) or OPUS (neither parent survived to age 95). Subjective and objective measures of physical function were compared between the two groups, accounting for potential confounders. Of the 893 LonGenity subjects, 365 were OPEL and 528 were OPUS. OPEL had better objective and subjective measures of physical function than OPUS, especially on unipedal stance (p = 0.009) and gait speed (p = 0.002). Results support the protective role of exceptional parental longevity in preventing decline in physical function, possibly via genetic mechanisms that should be further explored.     

Improving the reliability and reporting of genetic association studies

Genetic association studies, in particular candidate gene studies, have a long history of initially promising findings which subsequently produce a confusing mixture of replications, partial replications and non-replications. Drug and Alcohol Dependence is receiving an increasing number of submissions of genetic association studies. Here we discuss the journal's approach to considering such papers, in order to encourage credible and balanced reports which will contribute positively to the field. Recently, the STrengthening the REporting of Genetic Association studies (STREGA) initiative has provided guidelines which serve to enhance transparency. We strongly encourage authors considering submitting a genetic association study to the journal to follow these guidelines.     

Analysis of the S810L Point Mutation of the Mineralocorticoid Receptor in Patients with Pregnancy‐Induced Hypertension

Objective. A missense mutation at codon 810 (Ser → Leu) of the mineralocorticoid receptor was recently observed in a family with early manifestation of hypertension. Our objective was to determine if this mineralocorticoid receptor alterations is prevalent in patients with pregnancy‐induced hypertension. Methods. Thirty‐eight women with hypertension during pregnancy were tested for the mineralocorticoid receptor gene mutation. DNA was extracted out of blood leucocytes. PCR and automated DNA sequencing were used to analyze exon 6 for the S810L missense mutation. Anamnestical data concerning cardiovascular risk factors and family history were evaluated with a questionnaire. Pregnancy course and outcome were documented in all cases. Results. In 33 patients with pregnancy‐induced hypertension and in five patients with exacerbation of preexisting hypertension in pregnancy no point mutations were found at codon 810 in exon 6. Conclusions. Our data suggest that the S810L missense mutation of the mineralocorticoid receptor does not play a major role in the etiology of pregnancy‐induced hypertension in a German /Turkish population.     

Alcances de la aleatorización mendeliana para el control de confusores no observables en epidemiología

The Mendelian randomization is an epidemiologic method proposed to control for spurious associations in observational studies. These associations are commonly caused by confusion derived from social, environmental, and behavioral factors, which can be difficult to measure. Mendelian randomization is based on the selection of genetic variants that are used as instrumental variables that influence exposure patterns or are associated with an intermediate phenotype of the disease. The present work aims to discuss how to select the appropriate genetic variants as instrumental variables and to present methodological tools to deal with the limitations of this epidemiological method. The use of instrumental variables for modifiable exposures has the potential to mitigate the effects of common limitations, such as confusion, when robust genetic variants are chosen as instrumental variables.     

Rolandic癫痫的遗传病学研究进展

Rolandic癫痫(RE)又称儿童良性癫痫伴中央颞区棘波(BECTS),是最常见的儿童特发性癫痫综合征。既往认为,RE预后通常良好,常在青春期以前自行缓解。1982年,Aicardi和Chevrie提出RE变异型(ARE)的概念,指部分RE患儿起病初期的临床及电生理表现符合RE的特点,但在病程的演变过程中,临床和脑电图出现恶化。目前认为RE是从轻型至严重脑功能损害的连续性癫痫失语谱系疾病(EAS),常伴不同程度的认知和言语功能障碍。RE谱系疾病病因复杂,发病机制仍不完全清楚。随着分子遗传学的发展,近年发现该谱系疾病为复杂多基因遗传和环境因素共同致病,并发现多个基因与其相关。现重点关注RE谱系疾病的遗传学最新进展,从相关基因分子生物学特点、变异与RE谱系疾病的临床相关性及变异的功能学研究3个方面进行详细阐述,以帮助RE癫痫谱系疾病的临床基因报告解读和临床诊断。