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Emerging evidence is examining the precise role of intestinal microbiota in the pathogenesis of type 2 diabetes. The aim of this study was to investigate the association of intestinal microbiota and microbiota-generated metabolites with glucose metabolism systematically in a large cross-sectional study in China. 1160 subjects were divided into three groups based on their glucose level: normal glucose group (n=504), prediabetes group (n=394), and diabetes group (n=262). Plasma concentrations of TMAO, choline, betaine, and carnitine were measured. Intestinal microbiota was measured in a subgroup of 161 controls, 144 prediabetes and 56 diabetes by using metagenomics sequencing. We identified that plasma choline [Per SD of log-transformed change: odds ratio 1.36 (95 confidence interval 1.16, 1.58)] was positively, while betaine [0.77 (0.66, 0.89)] was negatively associated with diabetes, independently of TMAO. Individuals with diabetes could be accurately distinguished from controls by integrating data on choline, and certain microbiota species, as well as traditional risk factors (AUC=0.971). KOs associated with the carbohydrate metabolism pathway were enhanced in individuals with high choline level. The functional shift in the carbohydrate metabolism pathway in high choline group was driven by species Ruminococcus lactaris , Coprococcus catus and Prevotella copri. We demonstrated the potential ability for classifying diabetic population by choline and specific species, and provided a novel insight of choline metabolism linking the microbiota to impaired glucose metabolism and diabetes. [ABSTRACT FROM AUTHOR]

Chronic exposure to noise is a detrimental environmental factor that can contribute to occupational noise-induced deafness (ONID) in industrial workers. ONID is caused by both environmental and genetic factors, and negatively impacts workers and manufacturing industries in China. Polymorphisms in the paraoxonase 2 gene (PON2) is associated with noise-induced hearing loss, and PON3 expression may modulate oxidative stress in cells and tissues by reducing the levels of reactive oxygen species, which are prominent in ONID. We conducted a matched case-control study to investigate whether PON3 polymorphisms and activity were associated with susceptibility to ONID. We genotyped PON3 single nucleotide polymorphisms (SNPs) using Sanger sequencing and measured the plasma PON3 activity using enzyme-linked immunosorbent assay. Conditional logistic regression models were fitted to evaluate the potential risk factors of ONID. A total of 300 subjects were included (n = 150 ONID and n = 150 control cases) from October 2017 to October 2019. We identified two types of genotypes for the PON3 SNPs. The independent risk factors for ONID were genotype CT and allele C with Odd's ratio (OR) = 2.12 (95% confidence interval [CI]: 1.18–3.84) and OR = 1.68 (95% CI: 1.06–2.66) for SNP rs11767787; AG and allele A with OR = 2.09 (95% CI: 1.25–3.47) and OR = 1.87 (95% CI: 1.19–2.93) for SNP rs13226149; and CT and allele T with OR = 2.59 (95% CI: 1.44–4.67) and OR = 1.95 (95% CI: 1.22–3.14) for SNP rs17882539, respectively. Furthermore, the plasma PON3 level (> 1504 U/L) was observed to be a protective factor associated with the lowest level of ONID (less than 991 U/L) after adjusting for confounding factors (OR = 0.27, 95% CI: 0.13–0.54). In conclusion, the PON3 polymorphisms rs11767787, rs13226149, and rs17882539 and plasma PON3 activity are associated with susceptibility to ONID in the Chinese population. [ABSTRACT FROM AUTHOR]

Prenatal organophosphate pesticide (OP) exposure was reported to negatively affect childhood neurodevelopment. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of OPs and may affect an individual's susceptibility to OP exposure. However, little is known about its role in the associations of prenatal OP exposure and childhood neurodevelopment. We measured dimethylphosphate (DM), diethylphosphate (DE), and total dialkylphosphate (DAP) metabolites in maternal urine (n = 436) as well as PON1–108C/T and PON1192Q/R genotypes in maternal blood (n = 244). We assessed the modifying effects of maternal PON1–108C/T and PON1192Q/R genotypes on relationships between prenatal OP exposure and developmental quotients (DQs) in 24-month-old children in Shandong, China (n = 172). Among children of mothers carrying PON1–108CC, a tenfold increase in prenatal DMs was associated with a 5.72-point decrease in social domain DQ scores. Among children of mothers carrying PON1192QQ, a tenfold increase in prenatal DMs and DAPs were associated with a 7.68- and 7.67-point decrease in gross motor domain DQ scores, respectively. Among children of mothers carrying PON1192QQ, a tenfold increase in prenatal DMs, DEs, and DAPs were associated with a 7.52-, 9.07-, and 9.60-point decrease in social domain DQ scores, respectively. Maternal PON1 genotype might modify the associations between prenatal OP exposure and children's neurodevelopment at 24 months of age. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 376–383 (2010) Aims To examine the independent and joint effects of multiple genetic variants on a cardiac end-point in an 8-year prospective study of a Chinese diabetic cohort. Methods Seventy-seven single nucleotide polymorphisms (SNPs) of 53 candidate genes for inflammation, thrombosis, vascular tone regulation and lipid metabolism were genotyped in 1297 Chinese patients with no prior history of coronary heart disease (CHD) or heart failure at baseline. Cardiac end-point was defined by the occurrence of CHD and/or heart failure. Results In Cox regression model, after adjustment for baseline confounding variables including age, sex, smoking status, duration of diabetes, glycaemic control, lipid levels, waist circumference, blood pressure, albuminuria and estimated glomerular filtration rate, genetic variants, including Ala/Ala of SCYA11 (eotaxin) Ala23Thr, Cys/Cys or Cys/Ser of PON2 (paraoxonase 2) Ser311Cys and Arg/Arg of ADRB3 (β3-adrenergic receptor) Trp64Arg, were independently associated with incident cardiac end-point, with respective hazard ratios (95% confidence interval) of 1.70 (1.10–2.61, P = 0.037), 1.42 (1.08–1.88, P = 0.013) and 3.84 (1.18–12.50, P = 0.025). Analysis of the joint effect of the risk alleles showed significant increased risk of the cardiac end-point with increasing number of risk alleles ( P < 0.001). The adjusted risk for the cardiac end-point was 4.11 ( P = 0.002) for patients carrying four risk alleles compared with those carrying one or no risk allele. Conclusions The independent risk conferred by genetic variants encoding pathways such as inflammation and lipid metabolism, not adequately reflected by conventional biomarkers, may identify high-risk individuals for intensified control of modifiable risk factors. [ABSTRACT FROM AUTHOR]