MassARRAY multigene screening combined with LDL-C and sdLDL-C detection for more favorable outcomes in type 2 diabetes mellitus therapy.

BACKGROUND: To determine the clinical value of multigene polymorphisms, LDL-C and sdLDL-C on T2DM therapy. METHODS: In total, 352 T2DM patients before and after treatment and 48 healthy individuals were enrolled in this study. LDL-C and sdLDL-C were detected in 352 T2DM patients and 48 healthy individuals by Quantimetrix Lipoprint System. The 11 gene polymorphisms-HTR3B (rs2276307, A > G), APOE (rs7412, c.526C > T), APOE (rs429358, c.388 T > C), CYP2C9*3 (rs1057910, c.1075A > C), KIF6 (rs20455, c.2155 T > C), HMGCR (rs17238540, T > G), HMGCR (rs17244841, A > T), ABCB1 (rs2032582, A > C/T), HTR7 (rs1935349, C > T), SLCO1B1 (rs4149056, c.521 T > C), and CETP (rs708272, G > A)-were screened in these 352 T2DM patients by the Agena Bioscience MassARRAY system before therapy. RESULTS: Genetic polymorphisms associated with T2DM and statin effects in pretreatment patients were detected, then results showed that all 11 genes had heterozygous mutation, and 7 genes had homozygous mutation in 352 T2DM patients, more specifically reflected that these gene polymorphisms were common in Chinese T2DM patients. LDL-C and sdLDL-C were detected before and after treatment, sdLDL mainly existed in T2DM patients, and T2DM patients had higher mean levels of sdLDL-C than healthy people. After pharmacotherapy, the coincidence rates of decreases in LDL-C and sdLDL-C levels were 88.35% (311/352) and 84.09% (296/352), consistent with patients in remission. CONCLUSIONS: Gene polymorphisms related to pharmacotherapy were common in Chinese T2DM patients. And the expression of LDL-C and sdLDL-C was consistent with the T2DM disease course. Combined multigene screening before therapy and LDL-C and sdLDL-C detection before and after therapy could better assist T2DM treatment.

Comparison of machine learning tools for the prediction of AMD based on genetic, age, and diabetes-related variables in the Chinese population.

INTRODUCTION: Age-related macular degeneration (AMD) is the main cause of visual impairment and the most important cause of blindness in older people. However, there is currently no effective treatment for this disease, so it is necessary to establish a risk model to predict AMD development. METHODS: This study included a total of 202 subjects, comprising 82 AMD patients and 120 control subjects. Sixty-six single-nucleotide polymorphisms (SNPs) were identified using the MassArray assay. Considering 14 independent clinical variables as well as SNPs, four predictive models were established in the training set and evaluated by the confusion matrix, area under the receiver operating characteristic (ROC) curve (AUROC). The difference distributions of the 14 independent clinical features between the AMD and control groups were tested using the chi-squared test. Age and diabetes were adjusted using logistic regression analysis and the "genomic-control" method was used for multiple testing correction. RESULTS: Three SNPs (rs10490924, OR = 1.686, genomic-control corrected p-value (GC) = 0.030; rs2338104, OR = 1.794, GC = 0.025 and rs1864163, OR = 2.125, GC = 0.038) were significant risk factors for AMD development. In the training set, four models obtained AUROC values above 0.72. CONCLUSIONS: We believe machine learning tools will be useful for the early prediction of AMD and for the development of relevant intervention strategies.

Identification and functional characterization of a novel selenocysteine methyltransferase from Brassica juncea L.

Organic selenium (Se), specifically Se-methylselenocysteine (MeSeCys), has demonstrated potential effects in human disease prevention including cancer and the emerging ameliorating effect on Alzheimer's disease. In plants, selenocysteine methyltransferase (SMT) is the key enzyme responsible for MeSeCys formation. In this study, we first isolated a novel SMT gene, designated as BjSMT, from the genome of a known Se accumulator, Brassica juncea L. BjSMT shows high sequence (amino acid) similarity with its orthologues from Brassica napus and Brassica oleracea var. oleracea, which can use homocysteine (HoCys) and selenocysteine (SeCys) as substrates. Similar to its closest homologues, BjSMT also possesses a conserved Thr187 which is involved in transferring a methyl group to HoCys by donating a hydrogen bond, suggesting that BjSMT can methylate both HoCys and SeCys substrates. Using quantitative real-time PCR (qRT-PCR) technology and BjSMT-transformed tobacco (Nicotiana tabacum) plants, we observed how BjSMT responds to selenite [Se(IV)] and selenate [Se(VI)] stress in B. juncea, and how the phenotypes of BjSMT-overexpressing tobacco cultured under selenite stress are affected. BjSMT expression was nearly undetectable in the B. juncea plant without Se exposure, but in the plant leaves it can be rapidly and significantly up-regulated upon a low level of selenite stress, and enormously up-regulated upon selenate treatment. Overexpression of BjSMT in tobacco substantially enhanced tolerance to selenite stress manifested as significantly higher fresh weight, plant height, and chlorophyll content than control plants. In addition, transgenic plants exhibited low glutathione peroxidase activity in response to a lower dose of selenite stress (with a higher dose of selenite stress resulting in a high activity response) compared with the controls. Importantly, the BjSMT-transformed tobacco plants accumulated a high level of Se upon selenite stress, and the plants also had significantly increased MeSeCys production potential in their leaves. This first study of B. juncea SMT demonstrates its potential applications in crop MeSeCys biofortification and phytoremediation of Se pollution.

Association of the manganese superoxide dismutase gene Ala-9Val polymorphism with age of smoking initiation in male schizophrenia smokers.

Schizophrenia patients exhibit higher smoking rates than the general population. A growing body of evidence suggests that cigarette smoke impairs the antioxidant defense mechanisms, leading to oxidative damage. Manganese superoxide dismutase (MnSOD) is the major antioxidant in the mitochondria, catalyzing the metabolism of superoxide radicals to form hydrogen peroxide. Since the identification of a well-characterized functional polymorphism, Ala-9Val of MnSOD, a number of studies have evaluated the association between Val-9Ala and schizophrenia or cancer. In this study, we hypothesized that the functional polymorphism of MnSOD Ala-9Val was associated with smoking in patients with schizophrenia. This polymorphism was genotyped in 666 chronic male schizophrenia patients (smoker/never-smoker = 507/159) and 660 male controls (smoker/never-smoker = 360/300) using a case-control design. The cigarettes smoked per day (CPD) and smoking behaviors were evaluated by clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence (FTND). The results showed no significant differences in MnSOD Ala-9Val genotype and allele distributions between the patients and healthy controls or between smokers and never-smokers in either patients or healthy controls alone. The smokers with the Ala allele started smoking significantly earlier (19.9 ± 5.8 vs. 21.7 ± 6.5 years, P = 0.005) only in patients. These results suggest that the MnSOD Ala-9Val polymorphism may not influence smoking status in a Chinese male schizophrenia population, but may influence the age at which smoking is started among schizophrenia smokers.