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简介：AIMHumanglutathioneS-transferaseA1(GSTA1)isanimportantphaseⅡmetabolizingenzymeinvolvedinthemetabolismofmanytherapeuticdrugsandisresponsibleforthemetabolicdetoxificationofnumerouspromutagensandprocarcinogens.ThegeneticpolymorphismofGSTA1hasimportantimplicationsfordrugefficacyandcancersusceptibility.Inthisstudy,wedeterminedthedistributionofGSTA1geneticpolymorphisminMainlandChinese.Andwealsoinvestigatedwhetherthereexiststhepotentialphenotypealterationscausedbythegeneticpolymorphisminhuman.METHODSGenomicDNAwasex-tractedfromperipheralbloodof140Chinesepeopleand16livertissuesobtainedfromnon-liverishpatientswhounderwentpartialhepatectomy.AndthenthegenotypesofhumanGSTA1genewereanalyzedbypolymerasechainreaction-restrictedfragmentlengthpolymorphism(PCR-RFLP).

简介：AbstractObjective:He-Zhao deficiency was originally described as a severe type of nonsyndromic hypodontia, and the causative gene locus was mapped to chromosome 10q11.2. The aim of this study was to identify potential genetic mutations that could cause He-Zhao deficiency.Methods:Patients with He-Zhao deficiency and their unaffected relatives of the large pedigree were investigated. The whole-exome sequencing using next-generation sequencing was employed to identify genetic variants. The data generated from the whole-exome sequencing using the Illumina Novaseq 6000 system were further analyzed by Burrows-Wheeler Aligner software, Sequence Alignment/Map tools and ANNOVAR tool. In vitro luciferase assay was used to investigate the effect of the detected mutation on gene expression. R environment was used to conduct t-tests. The study protocol was approved by the Research Ethics Committee of Bio-X Institutes, Shanghai Jiao Tong University (M2011004).Results:The exomes of five patients with He-Zhao deficiency and two of their unaffected relatives identified a mutation in PRKG1α as the molecular etiology of the disease. The variant c.-144 C>A of PRKG1 isoform 1 cosegregated with permanent tooth agenesis in 93 family members who were older than 12, at which time the primary teeth should have been replaced with permanent teeth. Functional studies suggested that the mutant allele promotes gene transcription by increasing its promoter activity.Conclusion:c.-144 C>A variant of PRKG1α involving odontoclast-associated root resorption is responsible for He-Zhao deficiency, unlike other forms of hypodontia, which typically involve odontoblast dysfunction.

简介：AbstractThere is increasing evidence that cell-free DNA (cfDNA) in spent culture media (SCM) can be amplified for genetic testing. Therefore, this paper reviews the characteristics of cfDNA, including its fragment size, amount, origin, as well as some factors affecting the success rate of its amplification, together to provide researchers with a more comprehensive perspective on embryonic cfDNA. The origin of cfDNA in SCM is complicated and poses challenges to the interpretation of genetic test results. Advanced molecular techniques should distinguish between embryonic and contaminated DNA to maximize the success rate of amplification and analysis. Recent data showed that the type of culture medium, assisted hatching or not, the type of amplification kit, and fresh or thawed embryos were not related to the success rate of amplification, but the length of culture time might affect the success rate. The longer culture time, the more cfDNA is available in the SCM. Then we focused on the concordance between trophectoderm (TE), inner cell mass, whole embryo, and embryonic cfDNA. Despite successful amplification, the concordance between TE and embryonic cfDNA was low. In summary, non-invasive genetic testing using SCM could represent a major advance in future single embryo selection, however, contamination and timing for media collection are key factors affecting the results, and current non-invasive cfDNA testing should not be directly applied to clinical practice. Further research is needed to improve the methods used for testing techniques and genetic analysis to achieve greater accuracy and trace its origins before it can be used in the clinics.

简介：BackgroundAlcoholdehydrogenase(ADH)andaldehydedehydrogenase2(ALDH2)arethekeyenzymesforalcoholmetabolism.SeveralgeneticstudieshaveinvestigatedtheassociationbetweenADHandALDH2geneticpolymorphismsandserumlipidprofile(SLP),however,theresultswereinconsistent.MethodsFourteenarticlesinvolving27,917participantswereincludedinthismeta-analysis.Weightedmeandifference(WMD)and95%confidenceintervals(CIs)werepresentedusingrandomeffectsmodel.PublicationbiaswasevaluatedbyfunnelplotandBegg’stest.Inaddition,tofurtherexploretheheterogeneity,subgroupanalysiswereperformed.ResultsOverall,therewasnoassociationbetweenADHgeneticpolymorphismsandSLPwithnoregardfordrinkingstatus.However,comparedwithALDH2wildhomozygousgenotype,ALDH2mutantgenotypeswereassociatedwithsignificantdecreaseinserumhighdensitylipoproteincholesterol(HDLC)(WMD-1.80mg/dL,95%CI-1.88to-1.72,P<0.001)andtotalcholesterol(TC)levels(WMD-1.10mg/dL,95%CI-1.59to-0.62,P<0.001),andsignificantincreaseinserumlowdensitylipoproteincholesterol(LDL-C)level(WMD0.30mg/dL,95%CI0.18to0.43,P<0.001).Althoughtherewasnosignificantdifferenceinserumtriglyceridelevelintheoverallpopulation,subgroupanalysisrevealedthatcomparedwithALDH2*1wildhomozygote,ALDH2*2alleledisplayedasignificantdifferenceinserumtriglyceridelevelbetweenthefemaleandmale(female:WMD1.69mg/dl,95%CI1.08to2.30,P<0.001;male:WMD-6.42mg/dL,95%CI-12.15to-0.68,P=0.028).ConclusionADHgeneticpolymorphismhasnoassociationwithSLP,regardlessofsexcategoryanddrinkingstatus.ALDH2geneticpolymorphismhasslightassociationwithHDL-C,LDL-CandTClevelsandsex-specificassociationwithserumtriglyceridelevel.WhetherornottheassociationbetweenADH2geneticpolymorphismsandSLPisresultedfromalcoholconsumptionneedsfurtherinvestigation.

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简介：AbstractObjective:To investigate the association of rs5210 in potassium voltage-gated channel subfamily J member 11 (KCNJ11) with gestational diabetes mellitus (GDM).Methods:Six hundred and thirty-two uncorrelated pregnancy females were recruited in Tongji hospital from October 2017 to June 2018, in which 241 pregnant women were identified as GDM, and 391 were non-GDM. All the pregnant women recruited in this study their peripheral venous blood of 5 mL were withdrawn, and DNA in the blood was extracted. rs5210 in KCNJ11 were genotyped using TaqMan Assays and genotype models were analyzed using logistic regression analyses.Results:After adjusting age and body mass index, the variant genotypes of rs5210 in genotype models were as follows: P for dominant model was 0.945, (odd ratio: 0.987, 95% confidence intervals (CI): 0.681-1.430); P for recessive model: 0.556, (odd ratio: 1.217, 95% CI: 0.633-2.343) and P for addictive model was 0.098 (genotype AA vs. GG), (odds ratio: 1.435, 95% CI: 0.936-2.201). Weight-gain during pregnancy and total cholesterol were significantly different in recessive model (P= 0.015, P= 0.022, respectively) of all participants.Conclusion:No significant association between gene susceptibility of rs5210 in KCNJ11 and GDM occurrence in Chinese pregnant women. But the variant of rs5210 was associated with weight-gain during pregnancy and total cholesterol blood levels. However, more cases are needed in genetic study to check its susceptibility with GDM occurrence in Chinese women.

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简介：AbstractBackground:Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) poses distinct clinical challenges due to extensively drug resistant (XDR) phenotype, and sequence type (ST) 11 is the most dominant blaKPC-2-bearing CP-Kp clone in China. The purpose of this current retrospective study was to explore the genetic factors associated with the success of XDR CP-Kp ST11 strains circulated in the intensive care unit (ICU) of a Chinese tertiary hospital.Methods:Six ST11 XDR CP-Kp strains were identified between May and December 2014 and validated by minimum inhibitory concentration examination, polymerase chain reaction, and pyrosequencing. The six ST11 XDR CP-Kp, as well as three multi-drug resistant (MDR) and four susceptible strains, were sequenced using single-molecule real-time method. Comprehensively structural and functional analysis based on comparative genomics was performed to identify genomic characteristics of the XDR ST11 CP-Kp strains.Results:We found that ST11 XDR blaKPC-2-bearing CP-Kp strains isolated from inpatients spread in the ICU of the hospital. Functionally, genes associated with information storage and processing of the ST11 XDR CP-Kp strains were more abundant than those of MDR and susceptible strains, especially genes correlative with mobile genetic elements (MGEs) such as transposons and prophages. Structurally, eleven large-scale genetic regions taken for the unique genome in these ST11 XDR CP-Kp strains were identified as MGEs including transposons, integrons, prophages, genomic islands, and integrative and conjugative elements. Three of them were located on plasmids and eight on chromosomes; five of them were with antimicrobial resistance genes and eight with adaptation associated genes. Notably, a new blaKPC-2-bearing ΔΔTn1721-blaKPC-2 transposon, probably transposed and truncated from ΔTn1721-blaKPC-2 by IS903D and ISKpn8, was identified in all six ST11 XDR CP-Kp strains.Conclusion:Our findings suggested that together with clonal spread, MGEs identified uniquely in the ST11 XDR CP-Kp strains might contribute to their formidable adaptability, which facilitated their widespread dissemination in hospital.

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简介：AbstractObjective:To evaluate the effect of preimplantation genetic testing for aneuploidy (PGT-A) in infertile patients with recurrent pregnancy loss (RPL).Methods:A prospective randomized clinical trial was performed in a university-affiliated fertility center in Shanghai, China. Patients in the PGT-A group underwent blastocyst biopsy followed by single-nucleotide polymorphism microarray-based PGT-A and single euploid blastocyst transfer, whereas patients in the control group underwent routine in vitro fertilization/ICSI procedures and frozen embryo transfer of 1-2 embryos selected according to morphological standards.Results:Two hundred and seven infertile patients with RPL were included in this study and randomly assigned to either the control or the PGT-A group. Baseline variables and cycle characteristics were comparable between the two groups. The results showed that PGT-A significantly improved the ongoing pregnancy rate (55.34% vs. 29.81%) as well as the live birth rate (48.54% vs. 27.88%) and significantly reduced the miscarriage rate (0.00% vs. 14.42%) on a per-patient analysis. A significant increase in cumulative ongoing pregnancy rates over time was observed in the PGT-A group. Subgroup analysis showed that the significant benefit diminished for patients who attempted ≥2 PGT-A cycles.Conclusions:PGT-A significantly improved the ongoing pregnancy and live birth rate, while reduced miscarriage rate in infertile RPL patients. However, the significance diminished in patients attempting ≥2 cycles; thus, further studies are warranted to explore the most cost-effective number of attempts in these patients to avoid overuse.