17q21 loci gene and childhood asthma / 国际儿科学杂志

Asthma,a chronic inflammatory airway disease,is influenced by both genetic and environmental factors.It is a complex disease that involves the interplay among multiple physiological processes.Currently,it has been identified that 17q21 loci genes especially orosomucoid like 3 (ORMDL3) and gasdermin B (GSMDB) are strongly linked with the susceptibility and severity of childhood asthma by using of the Genome-Wide Association Study (GWAS).Furthermore,a better understanding of the molecular mechanism contributes to the asthma target therapeutics and precision medicine.This review summarizes the 17q21 loci genes associated with the susceptibility,severity,and race specificities of childhood asthma.

Estrogen weakens muscle endurance via estrogen receptor-MAPK mediated orosomucoid suppression / 中国药理学与毒理学杂志

Gender differences in fatigue, manifesting as female more prone to feel exhausted with lower muscle endurance, still remains unclear mechanism. Here, we investigated whether orosomucoid, an endogenous anti-fatigue protein which can enhance muscle endurance, is involved in this regulation. Female rats showed lower muscle endurance, and this gender difference was disappeared in orosomucoid 1-deficient mice. Female rats also displayed weaker orosomucoid induction in serum, liver and muscle in response to fatigue when compared to male ones. Ovariectomy in female rats results in elevated orosomucoid level and increased swimming time which was reversed by estrogen replenishment, while exogenous estrogen treatment both in male or female mice produced opposite effects. In vitro C2C12 muscle and Chang liver cells, estrogen decreased orosomucoid expression and its promoter activity, and this effect was abolished when estrogen receptor or MAPK was blocked. Thus, estrogen negatively regulates orosomucoid expression, which is responsible for the weaker muscle endurance in females.

Effect of ORM1 genetic polymorphism on time-course of muscle relaxation induced by rocuronium / 中华麻醉学杂志

Objective To evaluate the effect of ORM1 genetic polymorphism on the time-course of muscle relaxation induced by rocuronium.Methods Seventy American Society of Anesthesiologists physical status [or Ⅱ patients,aged 25-55 yr,scheduled for elective gynecological laparoscopic surgery,with body mass index of 20-25 kg/m2,were enrolled in this study.Anesthesia was induced with iv midazolam and fentanyl and target-controlled infusion of propofol.After the patients lost consciousness,neuromuscular block was assessed with TOF Watch-SX using single stimulation of the ulnar nerve.When the maximal twitch depression was achieved,tracheal intubation was facilitated with rocuronium 0.6 mg/kg.The patients were mechanically ventilated.End-tidal carbon dioxide partial pressure was maintained at 35-45 mmHg.The onset time,nonresponse time,clinical duration,75％ recovery time and recovery index of rocuronium were recorded.Peripheral venous blood samples were collected before surgery for determination of concentrations of plasma alpha1 acid glycoprotein,C-reactive protein (by enzyme-linked immunosorbent assay)and albumin (by biochemical method).ORM1 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism.The patients were divided into 3 groups according to the ORM1 genotypes:wild homozygote (ORM1*F1/*F1) group (AA group),mutation heterozygote (ORM1'F1/*S)group (AG group) and mutation homozygote (ORM1*S/*S) group (GG group).Results There were 40 cases in group AA,25 cases in group AG,and 5 cases in group GG.There were no significant differences in plasma alphal acid glycoprotein,albumin and C-reactive protein concentrations between the three groups (P＞0.05).Compared with group AA,the clinical duration,75％ recovery time and recovery index of rocuronium were significantly prolonged (P＜0.05),and no significant change was found in the onset time and nonresponse time in AG and GG groups (P＞0.05).Conclusion ORM1 genetic polymorphism is one of the genetic factors which affect the time-course of muscle relaxation induced by rocuronium.

The mRNA expression and clinical significance of ORMDL3 gene in the peripheral blood of recurrent wheeze children / 中华实用儿科临床杂志

Objective To study the mRNA expression levels and clinical significance of omsomucoid 1-like protein 3 (ORMDL3) gene in the peripheral blood of recurrent wheeze children under 3 years old.Methods Peripheral blood specimens of 25 recurrent wheeze children including 14 non-atopy patients (group A) and 11 atopy patients (group B) that were registered in the First Affiliated Hospital of Nanjing Medical University,from Sep.2010 to Sep.2012 were enrolled based on the inclusion criteria and 24 non-allergic controls(the children with food allergy,drug allergy or ectema was excepted).The mRNA expression levels of ORMDL3 gene were detected by reverse transcription (RT)-PCR and clinical features were analyzed.Results The expression levels of ORMDL3 were up-regulated in the peripheral blood specimens of group B compared with group A (t =14.12,P ＜ 0.01).Compared with peripheral blood specimens from normal subjects,mRNA expression of ORMDL3 were significantly increased in recurrent wheeze children(t =10.29,5.73,P ＜0.01).The incidence of wheeze groups exist gender differences,male ＞ female.Wheeze usually with a high incidence in winter and spring.Conclusions The increase of ORMDL3 gene expression levels were correlated with recurrent wheeze under 3 years old especially in atopy group and may be involved in the pathogenesis of recurrent wheeze.

Expression of α1-antitrypsin and α1-glycoprotein in children with Wilms tumor and its clinical / 中国医师进修杂志

Objective To analyze the serumα1-antitrypsin (α1-AT) and α1-glycoprotein (α 1-AGP) in children with Wilms tumor,and to explore the clinical application value.Methods Thirtyeight children with Wilms tumor who received treatment from January 2007 to December 2010 were designed as observation group,38 healthy children were designed as control group.Fluorescence quantitative PCR was performed to analyze α 1-AT andα 1-AGP mRNA transcription levels of two groups,and ELISA was used to measure the serum concentration of α 1-AT and α 1-AGP.Results The mRNA levels of α 1-AT and α 1-AGP in observation group were 3.50 ± 0.37 and 2.10 ± 0.41,which were significantly higher than those in control group (0.90 ± 0.45,0.50 ± 0.24) (P =0.000,0.002).The levels of α 1-AT and α 1-AGP in observation group were (4516.8 ± 102.4),(1316.0 ± 27.3) g/L,which were significantly higher than those in control group [(2467.4 ± 23.8),(728.6 ± 9.4) g/L] (P =0.015,0.008).Conclusion To detect the levels of α 1-AT and α 1-AGP have the potential value for the diagnosis of Wilms tumor,which can be applied to early screening.

A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico

The human orosomucoid 1 gene (ORM1) codes an alpha-1-acid glycoprotein that has been classified as an acute-phase reactive protein, and a major drug-binding serum component, as well as an immunomodulatory protein with genetic polymorphisms. Evaluation of ORM variation through isoelectric focusing and immunobloting has revealed a world-wide distribution of the ORM1 F and ORM1 S alleles. We evaluated and examined the genetic characteristicsof two Mexican populations that have different anthropological and cultural antecedents, examining two ORM1 genotypes (exon 1 - A/G (Gln20Arg) and exon 5 G/A (Val156Met)) in 145 individuals, using nested polymerase chain reaction, sequencing, and restrited fragment length polymorphism. Mexican Mestizos had higher frequencies of the exon 1 A allele (P = 0.020) and AA genotype(P = 0.018) and lower frequency of the G allele (P = 0.020) when compared to Teenek Amerindians. When we examined exon 5 G/A (Val156Met) polymorphisms, we found significantly higher frequencies of the G allele (P = 0.0007) and the GG genotype (P = 0.0003) in the Mexican Mestizo population. The Teenek population had a significantly higher frequency of the A allele than has been reported for Chinese and African (P < 0.05) populations, and the G/A genotype was more frequently found in this Mexican population than in Chinese, African and European populations (P < 0.05).

SIMULTANEOUS PHENOTYPING OF ORM, PI, AHSG AND GC IN HUMAN BLOODSTAINS USING PAGE IEF IMMUNOASSAY / 中国法医学杂志

A PAGE IEF immunoassay was established to detect the ORM, Pi, AHSG and GC phenotypes slmultaneously in human bloodstains. The cumulative discriminating power and probability of paternity exclusion were 0. 9878 and 0. 6648 respectively. Human sera diluted 100 times and bloodstains kept at room temperature for 4 weeks could be typed for these four blood groups correctly. The phenotypes of ORM, AHSG and GC could be determined correctly in bloodstains kept at room temperature within 24 weeks. This provides a good approach for individual identification of human bloodstains.

PREPARATION OF ANTI-ORM SERA / 中国法医学杂志

?-1 acid glycoprotein, also named orosomucoid (ORM), is one kind of serum protein with genetic polymorPhism. Anti-ORM serum is necessary to phenotyping ORM. This communication describes the preparation of the antiORM serum. The anti-ORM sera were produced in three New Zealand rabbits cimmunized with ORM which was isolated and purified from human sera previously in our laboratory. The results of identification showed that the specificity of the home made anti-ORM and the commercial anti-ORM sera (Sigma) were identical. The titer of the home made anti-ORM serum was 128. 2.4?g/ml ORM could be detected by double immunodiffusion with the anti-ORM serum. In addition, the anti-ORM serum did not cross-react with other human serum proteins.