Association between two polymorphisms of the bone morpho- genetic protein-2 gene with genetic susceptibility to ossification of the posterior longitudinal ligament of the cervical spine and its severity

Background Ossification of the posterior longitudinal ligament （OPLL） has a strong genetic background. Previous studies have shown that bone morphogenetic protein-2 （BMP2） and BMP2 mRNA are expressed in ossifying matrix and chondrocytes adjacent to cartilaginous areas of OPLL tissues and mesenchymal cells with fibroblastic features in the immediate vicinity of the cartilaginous areas. It is suggested that BMP2 plays different roles in the different stages of development of OPLL. However, it remains unknown which factors induce ligament cells to produce BMP2. Methods OPLL patients （n=-192） and non-OPLL controls （n=304） were studied. Radiographs of the cervical spine were analyzed for extent of OPLL. We investigated whether single nucleotide polymorphisms of exons 3（-726） T/C and 3（-583） NG in the BMP2 gene are statistically associated with genetic susceptibility to OPLL in Chinese Han subjects. Results There was no statistical difference between the occurrence of exons 3（-726） T/C and 3（-583） NG and the occurrence of OPLL in the cervical spine. However, there was a significant association between occurrence of exon 3（-726） T/C polymorphism and occurrence of OPLL in males of cases and controls in the cervical spine. In addition, no significant association was found between the exons 3（-726） T/C and 3（-583） A/G with number of ossified cervical vertebrae in OPLL patients. Conclusions Exon 3（-583） A/G polymorphism in BMP2 gene is not associated with the occurrence and the extent of OPLL in the cervical spine. Chinese Han male patients with TC and CC genotypes in exon 3（-726） T/C have genetic susceptibility to OPLL but not to more extensive OPLL in the cervical spine.     

中国汉族人群中20p12染色体上三个单核苷酸多态性与后纵韧带骨化发生及其严重程度的关系研究

Background Ossification of the posterior longitudinal ligament （OPLL） is characterized by the replacement of ligamentous tissue with new ectopic bone formation, and has a strong genetic background. Because of the abnormal bone metabolic features and the strong genetic component, osteoporosis is a related disorder with OPLL. Three polymorphisms on chromosome 20p12 were identified associated with the risk of osteoporosis and osteoporotic fracture.The rs996544 （C/T） ＂TT＂ and rs965291 （G/A） ＂AA＂ genotypes conferred higher risks for vertebral and hip fractures. The osteoporosis haplotype is defined by two polymorphisms, rs1116867 （A） and D35548 （T）. However, it remains unknown whether these three polymorphisms predispose to an increased frequency and severity of OPLL in Han Chinese patients.Methods A total of 420 OPLL patients and 506 age- and sex-matched controls were studied. Three single nucleotide polymorphisms （SNPs）, rs996544 （C/T）, rs965291 （G/A） and rs1116867 （A/G）, were analyzed by direct sequencing.Associations between these SNPs with the occurrence and extent of OPLL were statistically evaluated.Results There was no significant association between the rs996544 （C/T） polymorphism and the prevalence of OPLL.The rs1116867 （A/G） polymorphism ＂AG＂ genotype was associated with the occurrence of OPLL. The rs1116867 （A/G） polymorphism ＂G＂ allele was associated with the occurrence of OPLL, but not with the extent of OPLL. The rs965291 （G/A） polymorphism in female patients was statistically different between cases and controls （P 〈0.05）. The rs965291 （G/A） polymorphism ＂A＂ allele was associated with the occurrence of OPLL in female patients. For the rs965291 （G/A）polymorphism, patients with the ＂A＂ allele （genotype, ＂AG＂ or ＂AA＂） showed a significantly greater number of ossified cervical vertebrae than those without the ＂A＂ allele （genotype, ＂GG＂, P 〈0.05）, particularly in female patients.Conclusions The rs1116867 （A/G） and rs965291 （G/A） polymorphisms on chromosome 20p12 are associated with the occurrence and the extent of OPLL, at least in Han Chinese subjects. Our data should advance our understanding of the molecular etiology of OPLL and may guide approaches to prevent the onset of OPLL.     

No association between thrombospondin-4 A387P polymorphism and acute coronary syndrome in Chinese Han population

Objective： The thrombospondin-4 （TSP-4） gene G29926C （A387P） polymorphism was recently reported to be associated with an increased risk of MI （myocardial infarction） in American population. However, several subsequent studies produced controversial findings. The aim of this study was to explore the possible association between TSP-4 A387P polymorphism and ACS （acute coronary syndrome） in Chinese Han population. Methods：A case-control study including 412 patients with ACS and 337 controls free from CAD （coronary artery disease） was conducted. TSP-4 A387P polymorphism was determined by PCR （polymerase chain reaction） and RFLP （restriction fragment length polymorphism） analysis. Results：Slightly decreased frequency of GC genotype was observed in patients with ACS, compared with controls（5.3% vs. 7.1%）, but the difference did not reach statistical significance （P = 0.31 ）. Similarly, the prevalence of C allele was 2.7% and 3.6% for ACS and control groups, respectively （P = 0.32）. None of homozygote was detected for C allele. Further analyses in subjects subgrouped according to sex and age also showed no association of TSP-4 A387P polymorphism with ACS. Furthermore, after adjustment for conventional risk factors by multiple logistic regression analysis, the carrier prevalence of C allele did not differ significantly between ACS and control groups （OR = 0.85; 95% CI：0.45-1.59; P = 0.60）. Conclusion：The present study suggested that the TSP-4 A387P variant showed a low prevalence compared with western populations and failed to associate with an altered risk of ACS in Chinese Han population. The findings further supplement experimental data for TSP-4 gene study of coronary disease.     

遗忘型轻度认知功能损害患者认知特征与低密度脂蛋白受体相关蛋白1基因的关联研究

Objective To investigate the relationship between neuropsychological characteristics and low density lipoprotein receptor related protein 1 (LRP1) gene C766T polymorphism in amnestic mild cognitive impair-ment (Amci). Methods 109 Amci patients and 104 matched normal controls were recruited for the study. Multi-dimension neuropsychologic tests were used to extensively assess the cognitive function. Assay-on-demand was used to analyse LRP1 gene C766T polymorphism in the subjects. Results The scores of neuropsychologic tests in Amci patients were significantly lower than those in the normal controls ( all P<0.01), with the largest im-pairment on 20 minute delayed recall of the auditory verbal memory test (AVMT) ,which reflects episodic memory [Amci patients :3 (0-4) ,normal controls :7.5 (6～12), Z=-12.697, P<0.01]. No significant differences were found for the genotype and allele distribution of C766T polymorphism between Amci patients and the normal controls. C766T polymorphism was not associated with cognitive assessment scores in Amci patients (P>0.05). Conclusion Amci is characterized by episodic memory impairment;and LRP1 gene C766T polymorphism may not be an important genetic factor in susceptibility to aMCI.     

Novel mutation and polymorphism of PRSS1 gene in the Chinese patients with hereditary pancreatitis and chronic pancreatitis

Background Mutations in the cationic trypsinogen gene （PRSS1） have been detected in patients with hereditary pancreatitis （HP）. This study investigated the prevalence of the R122H （c.365G〉A）, A121T （c.361 G〉A） and D162D （c.488 C〉T） mutations or polymorphisms in the common, non-hereditary forms of chronic pancreatitis and in an HP family.
Methods DNA was prepared from blood samples of 54 patients with chronic pancreatitis （35 alcoholic, 17 idiopathic and 2 hereditary） and 120 normal controls. The PRSS1 genes were amplified by polymerase chain reaction （PCR） and their products were analyzed by sequencing and related clinical data were also collected.
Results A new polymorphism （c.488 C〉T） of PRSS1 was found in 25 patients with chronic pancreatitis （including one affected member of the HP family） and six members of the normal controls. The C/T genotype was significantly increased in chronic pancreatitis （OR： 16.379, 95% CI： 5.7522-52.3663）, the frequency of c.488 C〉T change was in according with the Hardy-Weinberg equilibrium, but it doesn＇t affect the clinical phenotype. The commonly reported change of R122H （c.365G〉A） was not detected in any of the study subjects, c.361 G〉A was found in 2 affected members and one unaffected carrier in an HP family. One of the affected members of an HP family had c.361 G〉A mutation and polymorphism （c.488 C〉T） in the PRSS1 gene at the same time. The patient＇s clinical values （C3, C4, CA19-9 and HbA1c） were higher than those of the other patients with chronic pancreatitis. The two patients with HP developed diabetes mellitus and their father died with pancreatic cancer.
Conclusion A new polymorphism （c.488 C〉T） in the PRSS1 gene is associated with chronic pancreatitis, but it did not affect the clinical phenotype while the A121T （c.361 G〉A） mutation in the gene shows a significant correlation in the patients with HP.     

The association between RASSF1 gene polymorphisms and lung cancer susceptibility among people in Hubei Province of China

The relationship between Ala/Ser polymorphism in 133 codon of exon 3 region of the RASSF1 gene and genetic susceptibility of lung cancer in Hubei province Han population was investigated by a case-control study. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique was adopted to analyze the polymorphism of codon 133 of exon 3 in the RASSF1 gene of 100 pathologically diagnosed lung cancer patients, and 100 healthy controls. The relationship between different genotypes and the susceptibility of lung cancer was analyzed. Among 200 blood samples from Han people in Hubei Province, including 100 from lung cancer patients and 100 from healthy controls, the frequencies of Ala/Ala, Ala/Ser, Ser/Ser genotype of the RASSF1 in lung cancer patients were 83%, 16%, 1%, and those in healthy controls was 93%, 7%, 0% respectively, with the difference being statistically significant between two groups （P〈0.05）. The individuals with Ala/Ser genotype had higher risk of suffering from lung cancer, with an OR of 2.341, and 95% CI of 1.009-6.393 respectively. It was concluded that RASSF1Ala133Ser was a susceptible genetic factor of lung cancer. Ala/Ser genotype increased the risk of lung cancer.     

ANP T2238C, C-664G Gene Polymorphism and Coronary Heart Diseasein Chinese Population

The association between atrial natriuretic peptide (ANP) polymorphism and coronary heart disease (CHD) was studied in Chinese population. The genotypes of ANP T2238C and ANP C-664G were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) methods in 158 consecutive CHD patients and 165 controls. It was found that the distribution of A2A2 genotype in CHD group was significantly higher than that in control group (P<0.05). Stepwise Logistic regression analysis revealed that male, smoking, history of hypertension, history of diabetes, family history of hypertension, high level of serum cholesterol, and ANP T2238C polymorphism were the possible risk factors in patients with CHD (P<0.05). However, there was no significant difference between the patients with CHD and the control group in the distribution of ANP C-664G polymorphism (P>0.05). The results suggest that A2A2 T2238C genotype could be one of the risk factors for CHD (P<0.05, OR: 1.80, 95 % CI: 1.03-3.15).     

Neck

<正>209193 The role of MR T2image signal intensity and clinical manifestations in predicting prognosis for cervical ossification of the posterior longitudinal ligament/Shen Yong(Dept Spinal Surg,3rd Hosp Hebei Med Univ,Shijiazhuang 050051)…∥Chin J Orthop.-2009,29(3).-212~215Objective To investigate whether the signal intensity ratio on MRI and clinical manifestations can reflect prognosis in patients with cervical ossification of the posterior longitudinal ligament (OPLL).Methods From February 1999 to July 2007,58 patients with cervical OPLL were prospectively enrolled.They were treated with posterior decompression and followed up 1 to 7 years.1.5 T MRI was performed in all patients before surgery.T2 weighted images (T2WI) of sagital signal intensity on the cervical severe compression cord were obtained,and the regions of interest(ROIs) were taken by 0.05 cm2.T2WI of sagittal normal cord signal on the cervical between C7T1 disc levels were obtained,and the ROIs were taken by 0.3 cm2.Signal value was measured by computer and the signal ratio between regions of the 0.05 cm2 and 0.3 cm2 had been calculated.All of 58 patients have been divided into three groups with signal intensity ratio.Statistical analysis were performed.Results There were significant differences between three groups at the recovery rate,age,duration of disease,Babinski sign,ankle clonus,preoperative JOA score and postoperative JOA score.There was no significant differences at gender in three groups.And multiple linear regression showed that the recovery rate was correlated with age,Babinski sign,duration of disease and ankle clonus.     

The association analysis of FcεRⅠβ with allergic asthma in a Chinese population

Objective To investigate the link between the polymorphism of -109 and Glu237 in the high-affinity IgE receptor β （FcεRⅠβ） gene and susceptibilty to allergic asthma in a Chinese population.Method Blood samples from 216 allergic asthma patients and 198 age- and sex-matched controls were studied. A-109C/T and a coding variant Glu237Gly in FcεRⅠβ were detected with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Results The genotype frequencies were 0.403 for -109T/T, 0.491 for －109T/C and 0.106 for －109C/C in allergic asthma in a Chinese population. No significant difference in the distribution of －109C/T polymorphism was found between allergic asthma subjects and healthy controls, however, homozygosity for the －109T allele was associated with increased total plasma IgE levels in subjects with allergic asthma (F=4.020,P&lt;0.05). The allele frequency of Gly237 in the patients and control was 0.236 and 0.136 respectively. There was a significant association between the Gly/Gly genotype and allergic asthma. Among allergic asthma patients Gly237 was significantly associated with high IgE levels.Conclusions These results suggest that the Gly237 variant of the FcεRⅠβ gene is involved in the development of allergic asthma. The-109C/T and Glu237Gly polymorphisms are two of the genetic factor identified thus far, which affect total plasma IgE levels of allergic asthma patients in a Chinese population.     

生物力学因素与BMP2单核苷酸多态性对颈椎后纵韧带骨化成骨作用的影响

目的 探讨生物力学因素与骨形态发生蛋白-2（bone morphogenetic protein 2,BMP2）单核苷酸多态性对颈椎后纵韧带骨化（ossification of the posterior longitudinal ligament,OPLL）成骨作用的影响,为进一步发现OPLL多因素共同致病的具体机制奠定基础.方法 采集颈椎OPLL病变组手术减压过程中骨化部位的后纵韧带和颈椎外伤等手术减压过程中的正常对照组后纵韧带.利用PCR和直接测序法分析BMP2上2个单核苷酸多态性位点109T＞G（rs2273073）,570A＞T（rs235768）基因型及等位基因型的分布.Masson三色染色观察组织学结构改变.免疫组织化学染色和Western blot法检测BMP2的分布和表达.用C3H10T1/2细胞做转染构建细胞模型：正常组、空载体组、BMP2野生型组、BMP2（rs2273073）单突变组、BMP2（rs235768）单突变组、BMP2（rs2273073,rs235768）双突变组.采用机械应力装置对接种于Flexercell板的细胞施加10％、0.5Hz的机械应力,持续加载24h.以同样接种于Flexereell板未施加机械应力的细胞作为对照组.采用Western blot法检测机械应力加载前后各组BMP2表达情况.结果 Masson三色染色组织学观察显示病变组有成骨结构改变,免疫组织化学染色和Western blot法显示病变组BMP2的表达增加.机械应力加载后,细胞转染模型BMP2（rs2273073）单突变组和BMP2（rs2273073,rs235768）双突变组的BMP2表达较未施加应力组明显增加,差异具有统计学意义（P＜0.05）.结论 BMP2单核苷酸多态性位点109T＞G（rs2273073）的突变不仅能提高人们对OPLL的易感性,同时能提高OPLL患者对机械应力的敏感度,从而加速OPLL的进展.     

颈椎后纵韧带骨化症经前路减压植骨融合术的麻醉处理

目的通过对比颈椎后纵韧带骨化症（ossification of posterior longitudinal ligament,OPLL）与非OPLL颈椎病经前路减压融合手术平均在每个节段所花的手术时间、出血量和输血量上的差异性,为完善麻醉方案提供参考依据。方法选择我院2007年1月—2008年12月的OPLL经前路减压融合手术患者17例和随机抽取30例非OPLL颈椎病（剔除肿瘤和外伤患者）经前路手术患者,分析平均在每个节段所花的手术时间、出血量和输血量上的差异性。结果OPLL比非OPLL颈椎病患者前路减压融合术平均在每个节段所花的手术时间明显要长（P〈0.01）、出血量显著增加（P〈0.01）。OPLL患者大部分需要输血,平均输血量约为850 ml,非OPLL患者基本不用输血。结论OPLL经前路手术所需时间比非OPLL颈椎病前路手术要长,出血量明显增加,大部分患者需要输血。因此,麻醉方案中应包括有创动脉血压监测、尿量监测和深静脉穿刺置管,多节段OPLL者术前必需充足备血。     

BMP-4基因上两个多态性位点与颈椎后纵韧带骨化症的关联性研究

目的通过测定颈椎后纵韧带骨化症患者与对照组骨形态发生蛋白-4上的2个单核苷酸多态性位点序列,探讨骨形态发生蛋白-4与颈椎后纵韧带骨化（OPLL）的遗传关联性。方法 OPLL病例组和正常对照组各200例,利用PCR和直接测序法分析骨形态发生蛋白-4（BMP4）上2个单核苷酸多态性位点6007C〉T（rs17563）,3564C〉T（rs2855532）基因型及等位基因型的分布。应用SPSS13.0软件进行统计学分析。检验水准α=0.05,如果P〈0.05认为有统计学意义。结果两组间位点rs17563,rs2855532基因型与等位基因型差异具有统计学意义（P=0.013,0.000）。OPLL组中rs17563带C等位基因型与不带C等位基因型骨化椎体数量差异具有统计学意义P〈0.001,前者骨化椎体数量明显少于后者;rs2855532T＋等位基因型（TT TC）与T-等位基因型（CC）骨化椎体数量差异也有统计学意义（P〈0.05）,前者骨化椎体数量多于后者。结论骨形态发生蛋白-4上的两个单核酸多态性位点rs17563,rs2855532等位基因型的突变与颈椎后纵韧带骨化症的发生和发展有关。     

新疆哈萨克族人神经前体细胞表达发育调控蛋白4基因遗传变异的分布及其与高血压的相关性

目的 探讨神经前体细胞表达发育调控蛋白4( NEDD4)基因功能区的多态位点与新疆哈萨克族人高血压病的相关性.方法 采取以流行病学调查为基础的病例对照研究,选择938例哈萨克族自然人群(包括451例高血压患者和487例对照)作为研究对象.首先测序筛查哈萨克族高血压病患者 NEDD4基因功能区的变异位点,选择代表性变异位点应用TaqMan-PCR在自然人群中进行基因型鉴定及病例对照关联研究.结果 在 NEDD4基因的功能区共发现13个新的和15个已知的变异位点,其中包括7个错义突变. NEDD4基因的9个代表性变异位点中,4个低频率的错义突变不是哈萨克族人高血压病特有的变异,5个常见单核苷酸多肽及其组成的各单倍型在高血压病例与对照组间的频率分布差异无显著性(P＞0.05).结论 NEDD4基因遗传变异与哈萨克族人高血压病无相关性.     

A single nucleotide polymorphism in the human bone morphogenetic protein-2 gene (109T>G) affects the Smad signaling pathway and the predisposition to ossification of the posterior longitudinal ligament of the spine

Background Although various systemic and local factors such as abnormal carbohydrate or calcium metabolism,aging,and hormonal disturbances have been suggested as causes of ossification of the posterior...     

新疆哈萨克族prostasin基因变异与原发性高血压的关联性

目的 探讨新疆哈萨克族prostasin基因变异与原发性高血压的关系.方法 采用整群随机抽样方式,以生活在新疆阜康市30岁以上的哈萨克族牧民938名为研究对象,进行标准化问卷调查、体格检查.根据2005年中国高血压防治指南选取研究对象:原发性高血压组451例,正常血压组487例.采用测序方法对prostasin基因所有外显子及启动子区测序;应用TaqMan PCR方法对代表性的变异(297A>C、2827C>T、E342K)进行基因分型,计算各基因型在两组中的分布频率.结果 发现10个变异位点:-36G>C,-27C>T,78G>A,81G>C(rs8049043),297A>C,350C>T,351A>C,2827C>T,3482G>A(E342K),3783A>G.对E342K和2827C>T成功分型,E342K突变仅有1例,且为原发性高血压患者.2827C>T多态性存在CC、CT、TT 3种基因型和C、T两种等位基因.3种基因型在原发性高血压病组和正常血压组中的频率分别为81.0%、17.3%、1.7%和80.3%、18.9%、0.8%,C、T等位基因频率分别为89.6%、10.4%和89.8%、10.2%,基因型和等位基因频率在两组间的差异均无显著性(χ~2=2.084,P=0.353和χ~2=0.001,P=0.973).各基因型之间血压水平的差异均无显著性(P>0.05).结论 Prostasin基因2827C>T多态性可能与原发性高血压发生无关;E342K突变可能部分参与新疆哈萨克族原发性高血压的形成.     

早发性帕金森综合征的PINK1基因变异分析

目的:探讨中国大陆汉族早发性帕金森综合征(early-onset Parkinsonism,EOP)患者PTEN诱导激酶1(PTEN-induced kinase 1,PINK1)基因突变特点.方法:在149例汉族EOP患者中应用DNA直接测序技术(DNA sequencing)检测PINK1基因点突变及小的插入/缺失...