N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), an oxidative derivative of tire anti-degradant, has been linked to mortality in coho salmon (Oncorhynchus kisutch) and has exhibited potential human toxicity. Hence, exploring how 6PPD-Q interacts with biomacromolecules like enzymes is indispensable to assess its human toxicity and elucidate its mechanism of action. This investigation aims to explore the impact of 6PPD-Q on lactate dehydrogenase (LDH) through various methods.
View Article and Find Full Text PDFAdiposity is an established risk factor for multiple diseases, but the causal relationships of different adiposity types with circulating protein biomarkers have not been systematically investigated. We examine the causal associations of general and central adiposity with 2923 plasma proteins among 3977 Chinese adults (mean BMI = 23.9 kg/m²).
View Article and Find Full Text PDFBackground: Higher body mass index (BMI) is associated with higher incidence of cardiovascular and some non-cardiovascular diseases (CVDs/non-CVDs). However, uncertainty remains about its associations with mortality, particularly at lower BMI levels.
Methods: The prospective China Kadoorie Biobank recruited >512 000 adults aged 30-79 years in 2004-08 and genotyped a random subset of 76 000 participants.
Lactate dehydrogenase (LDH), a crucial enzyme in anaerobic glycolysis, plays a pivotal role in the energy metabolism of tumor cells, positioning it as a promising target for tumor treatment. Rutin, a plant-based flavonoid, offers benefits like antioxidant, antiapoptotic, and antineoplastic effects. This study employed diverse experiments to investigate the inhibitory mechanism of rutin on LDH through a binding perspective.
View Article and Find Full Text PDFObjective: Integrated analyses of plasma proteomics and genetic data in prospective studies can help assess the causal relevance of proteins, improve risk prediction, and discover novel protein drug targets for type 2 diabetes (T2D).
Research Design And Methods: We measured plasma levels of 2,923 proteins using Olink Explore among ∼2,000 randomly selected participants from China Kadoorie Biobank (CKB) without prior diabetes at baseline. Cox regression assessed associations of individual protein with incident T2D (n = 92 cases).
Aims: Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition.
Methods And Results: In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C [PCSK9 genetic score (PCSK9-GS)].
Background: Genetic variants that affect alcohol use in East Asian populations could help assess the causal effects of alcohol consumption on cause-specific mortality. We aimed to investigate the associations between alcohol intake and cause-specific mortality using conventional and genetic epidemiological methods among more than 512 000 adults in China.
Methods: The prospective China Kadoorie Biobank cohort study enrolled 512 724 adults (210 205 men and 302 519 women) aged 30-79 years, during 2004-08.
Background: Although it is known that variation in the aldehyde dehydrogenase 2 (ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited.
Methods: We performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake.
Adiposity is associated with multiple diseases and traits, but little is known about the causal relevance and mechanisms underlying these associations. Large-scale proteomic profiling, especially when integrated with genetic data, can clarify mechanisms linking adiposity with disease outcomes. We examined the associations of adiposity with plasma levels of 1463 proteins in 3977 Chinese adults, using measured and genetically-instrumented BMI.
View Article and Find Full Text PDFThe China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving ∼5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history.
View Article and Find Full Text PDFPubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.
View Article and Find Full Text PDFOrganophosphate flame retardants (OPFRs) are newly emerging estrogenic environmental pollutants, which attracted widespread public interest owing to their potential threats to human. Here, the interaction between two typical aromatic OPFRs, TPHP/EHDPP and HSA was researched by different experiments. Experimental results indicated that TPHP/EHDPP can insert the site I of HSA and be encircled by several amino acid residues, Asp451, Glu292, Lys195, Trp214 and Arg218 played vital roles in this binding process.
View Article and Find Full Text PDFBackground And Aims: We investigated the causal relevance of alcohol intake with measures of carotid artery thickness and atherosclerosis in Chinese adults.
Methods: The study included 22,384 adults from the China Kadoorie Biobank, with self-reported alcohol use at baseline and resurvey, carotid artery ultrasound measurements, and genotyping data for ALDH2-rs671 and ADH1B-rs1229984. Associations of carotid intima media thickness (cIMT), any carotid plaque, and total plaque burden (derived from plaque number and size) with self-reported (conventional analyses) and genotype-predicted mean alcohol intake (Mendelian randomization) were assessed using linear and logistic regression models.