Association of TOMM40 Polymorphisms with Late-Onset Alzheimer’s Disease in a Northern Han Chinese Population

Mitochondrial dysfunction is an early defect in the pathogenesis of late-onset Alzheimer’s disease (LOAD). One interesting candidate gene for mitochondrial dysfunction in LOAD is the translocase of outer mitochondrial membrane 40 homolog (TOMM40) gene. Several single nucleotide polymorphisms (SNPs) within TOMM40 have been shown to affect susceptibility to LOAD in Caucasians, while there are no studies on the association of the polymorphisms with LOAD risk in Han Chinese. Here, the association of TOMM40 polymorphisms in LOAD was investigated in a large Northern Han Chinese cohort consisting of 1,578 individuals. Both allelic and genotypic associations of three SNPs (rs157580, rs2075650, and rs11556505) with LOAD risk were observed in the total sample as well as in the non- APOE ε4 carriers. For rs1160985, the allele and genotype frequencies differed significantly only in APOE ε4 carriers. After adjustment for age, gender, and APOE ε4 status, the association remained statistically significant only for the rs157580 but not for rs2075650 and rs11556505. In contrast, the rs1160985 exhibited significant risk effect after adjustment. In addition, haplotype analysis confirmed that the haplotypes derived from SNPs in rs2075650, rs11556505, and rs1160985 were associated with either risk or protective effects. In summary, our findings suggest that the TOMM40 polymorphisms may play a role in the pathogenesis of LOAD in Han Chinese.     

Decreased frontal lobe function in people with Internet addiction disorder

In our previous studies, we showed that frontal lobe and brainstem functions were abnormal in online game addicts. In this study, 14 students with Internet addiction disorder and 14 matched healthy controls underwent proton-magnetic resonance spectroscopy to measure cerebral function. Results demonstrated that the ratio of N-acetylaspartate to creatine decreased, but the ratio of cho- line-containing compounds to creatine increased in the bilateral frontal lobe white matter in people with Internet addiction disorder. However, these ratios were mostly unaltered in the brainstem, suggesting that frontal lobe function decreases in people with Internet addiction disorder.     

MCPH1 deletion in a newborn with severe microcephaly and premature chromosome condensation

A newborn with severe microcephaly and a history of parental consanguinity was referred for cytogenetic analysis and subsequently for genetic evaluation. While a 46,XY karyotype was eventually obtained, premature chromosome condensation was observed. A head MRI confirmed primary microcephaly. This combination of features focused clinical interest on the MCPH1 gene and directed genetic testing by sequence analysis and duplication/deletion studies disclosed a homozygous deletion of exons 1–11 of the MCPH1 gene. This case illustrates a strength of standard cytogenetic evaluation in directing molecular testing to a single target gene in this disorder, allowing much more rapid diagnosis at a substantial cost savings for this family.     

Epigenetic mechanisms in Alzheimer's disease: Implications for pathogenesis and therapy

The vast majority of Alzheimer's disease (AD) are late-onset forms (LOAD) likely due to the interplay of environmental influences and individual genetic susceptibility. Epigenetic mechanisms, including DNA methylation, histone modifications and non-coding RNAs, constitute dynamic intracellular processes for translating environmental stimuli into modifications in gene expression. Over the past decade it has become increasingly clear that epigenetic mechanisms play a pivotal role in aging the pathogenesis of AD. Here, we provide a review of the major mechanisms for epigenetic modification and how they are reportedly altered in aging and AD. Moreover, we also consider how aberrant epigenetic modifications may lead to AD pathogenesis, and we review the therapeutic potential of epigenetic treatments for AD.     

The Sociodemographic Characteristics,Periodontal Health Status,and Subgingival Microbiota of Patients With Chronic Periodontitis and Type 2 Diabetes Mellitus: A Case‐Control Study in a Chinese Population

Background: In China, chronic periodontitis (CP) is common in patients with type 2 diabetes mellitus (T2DM). The purpose of this study is to identify the sociodemographic characteristics associated with such patients and to assess the periodontal health status and subgingival microbiota of patients with CP and T2DM (T2DMCP) in the Chinese population. Methods: A total of 150 patients with T2DMCP and 306 patients with CP without any systemic disease completed questionnaires, underwent clinical periodontal examinations and participated in diabetes‐related parameter examinations. Subgingival plaques were obtained to determine the prevalence and amounts of selected oral bacterial species using polymerase chain reaction (PCR) and real‐time PCR, respectively. Results: The income level and mean body mass index (BMI) of the patients with T2DMCP were significantly higher than those of the patients with CP. Additionally, the patients with T2DMCP were more likely to be urban residents, and they had significantly more severe periodontitis than did the patients with CP. In the patients with T2DMCP, the prevalence and amounts of Treponema denticola and Tannerella forsythia were significantly higher than those in the patients with CP. Finally, compared with the patients with CP, the patients with T2DMCP had a significantly lower prevalence and amount of Prevotella intermedia. Conclusions: Compared with the patients with CP, the patients with T2DMCP were more likely to be urban residents and generally had higher incomes, higher mean BMI, and poorer periodontal health status. Higher levels of T. denticola and T. forsythia and lower levels of P. intermedia were identified in the subgingival plaque of the patients with T2DMCP.