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Objective To assess the association of tag single nucleotide polymorphisms ( tag SNPs) of SH2B adap-tor protein 3 ( SH2 B3 ) gene with essential hypertension ( EH ) in Han population .Methods Six tag SNPs ( rs7309325 , rs11065898 , rs10849947 , rs2239196 , rs2238154 and rs739496 ) were genotyped in 510 patients with EH and 510 healthy controls using polymerase chain reaction-restriction fragment length polymorphism method ( PCR-RFLP) .Results Compared to CC genotype , the T allele carriers of rs2239196 were more likely to be hy-pertensive ( OR=2.59 ,95%CI 1.36-4.96 ,Bonferroni correction P<0.05 ) .Conclusions The rs2239196 T al-lele is potential a risk factor of EH in Han population .
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To investigate the association of SH2B1 gene rs7359397 polymorphism with overweight and obesity,as well as some related metabolic indicators in Northwest Chinese. Based on the cohort of China National Diabetes and Metabolic disorders Study(2007-2008) in Shanxi province, totally 1210(including 635 overweight and 167 obese) males and 1711(including 781 overweight and 212 obese) females were participated in this study. Matrix assisted laser desorption/ionization time-of-flight mass spectrometry( MALDI-TOF MS) was adopted as the genotyping method. After adjusting for age, the single nucleotide polymorphism rs7359397 of SH2B1 was found to be associated with overweight and obesity in males. The correlation with overweight accords with the dominant(P=0. 02), overdominant(P=0. 03), and log-additive models(P=0. 025), while the correlation with obesity accords with the dominant(P=0. 0078), overdominant(P=0. 0081), and log-additive models(P=0. 015). rs7359397 showed to have a significant association with body mass index, body fat percentage, fasting serum insulin, homeostasis model assessment of insulin resistance in males;and high density lipoprotein-cholesterol in females(P<0. 05). The results show that SH2B1 rs7359397 polymorphism is associated with overweight, obesity, and related metabolic indicators in males of the population studied.
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Objective To observe the expression and influence of SH2-B in hepatocarcinoma,and to investigate the molecular mechanisms of canceration in hepatocarcinoma.Methods By using SABC imunohis-tochemistry,the expressions of SH2-B were detected in 27 cases of hepatitis,29 cases of hepatocirrhosis and 47 cases of hepatocarcinoma.Hepatocarcinoma cell (HepG)2 with a low-expressed SH2-B was selected using immunofluorescence assay.There were 3 groups:the transfected group (transfected with pcDNA3.1 -SH2-B), the vector group (transfected with pcDNA3.1 )and the blank group (without transfection).After gene transfec-tion,SH2-B expression was detected by Western blotting;cell proliferation was measured by MTT assay;cell colony was counted by colony formation test;and cell cycle was analyzed by flowcy tometer.Results The posi-tive rate of SH2-B in hepatocarcinoma (95.7%)was significantly higher than 55.2% in hepatocirrhosis (χ2 =1 8.64,P 82 ±8 in the vector group (t =-20.33,P <0.01 )and 78 ±9 in the blank group (t =-1 9.64,P <0.01 ), which indicated that the cell colony numbers increased after being transfected with SH2-B.The S stage cells of the transfected group was (45.7 ±5.8)%,significantly higher than (1 9.4 ±4.7)% in the vector group (t =-20.33,P <0.01 )and (20.5 ±5.1 )% in the blank group (t =-34.69,P <0.01 ),which indicated that SH2-B could enhance promote cell cycle of HepG2 cells.Conclusion The expression of SH2-B in hepatocar-cinoma is high,and it may be involved in the canceration of hepatocarcinoma though promoting cell cycle,cell proliferation and cell transformation.
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Objective In order to investigate the effect of SH2B1 on leptin signal transduction JAK2/IRS2 and its biological function.Methods Vitro kinase assay and Western blot were used to analyse tyrosine phosphorylatin of key molecule JAK2 and insulin receptor substrate-2 (IRS2). ELISA was used to measure the plasma leptin levels in mice. The postnatal growth of mice was monitored over 27 weeks. Results SH2B1 dramatically enhanced the leptin-stimulated tyrosine phosphorylation of JAK2 and IRS2 in HEK293 cells stably expressing LRb (HEK239~(LRb)). Leptin-stimulated activation of hypothalamic JAK2 and phosphorylation of hyphothalamic IRS2 were significantly impaired in SH2B1~(-/-) mice. The deletion of SH2B1 led to leptin resistance,and fasting and randomly fed plasma leptin levels were respectively 3.2 times and 5.1 times higher in SH2B1~(-/-) males than wild-type littermates at 15 weeks of age. SH2B1~(-/-) males gained body weight rapidly and exceeded wild-type littermates from 5~(th) week. SH2B1(-/-) (at 21 weeks) was approximately twice heavier than wild-type littermates.Conclusion SH2B1 is an endogenous enhancer of leptin sensitivity and required for maintaining normal bodyweight in mice via leptin JAK2/IRS2 pathway.
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Aim To explore the inhibitory effect of dexamethasone on the expression of SH2-B? in the lung and the visceral sensory afferent system(C7-T5 spinal ganglia and the corresponding posterior horn of the spinal cord)of asthmatic mice.Methods Murine model of asthma of BABL/c mice was induced by ovalbumin in vivo.By means of immunohistochemistry and Western blot,the expression of SH2-B? in the lung,C7-T5 spinal ganglia and corresponding spinal cord was detected and the inhibitory effect of dexamethasone on it was observed.Inspiratory airway resistance was measured with AniRes 2003 lung function system.Results The expression of SH2-B? in the lung,C7-T5 spinal ganglia and the corresponding spinal cord of the asthmatic mice was much higher than that of the control group and the dexamethasone group(P
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Objective:To study the effect of SH2-B? on asthma.Methods:After inhibition of SH2-B?,the cells in the bronchoalveolar lavage fluid(BALF) were counted,and IL-4 and IgE in BALF,sera and culture supernants of spleen cells were measured by means of ELISA.The changes of the airway resistance and lung function were analyzed by means of animal lungs function analysis system.Results:Compared with that of the asthmatic group,1)Airway resistance to methacholine(MCh) was decreased significantly in anti-SH2-B? group(P
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Objective To study the expression of SH2-B? in the lung and visceral sensory afferent system(C-7-T-5 spinal ganglia and the corresponding posterior horn of the spinal cord) of the asthmatic mice,and to explore the role of SH2-B? in asthma.Methods Thirty BALB/c mice were randomly divided into normal control group and asthmatic group on average.The alterations of SH2-B? and nerve growth factor(NGF)immunoreactivity were investigated by immunohistochemical and Western blotting method and analyzed by the Metamoph analysis system.Results Immunohistochemistry demonstrated that the mean optic density(MA)of SH2-B? positive substance in the lungs(0.806?0.023),C-7-T-5 spinal ganglia(0.766?0.014)and the corresponding posterior horn of the spinal cord(0.547?0.014)of the asthmatic mice was much higher than those(0.243?0.018,0.131?0.011,0.215?0.029) in normal control group respectively.Western blotting also demonstrated that SH2-B? and NGF expressions were more increased in the lungs and C-7-T-5 spinal cord of the asthmatic mice than those of normal control group.The mean ratio of SH2-B? MA to ?-actin MA in spinal cord and lung was 0.346?0.017 and 0.512?0.018 in normal control group,0.738?0.021 and 1.526?0.022 in asthmatic group.The mean ratio of NGF MA to ?-actin MA in spinal cord and lung was 0.357?0.021 and 0.734?0.013 in normal control group,1.445?0.015 and 1.265?0.018 in asthmatic group.A positive correlation was found between the levels of SH2-B? and NGF(r=0.651,P