整合素α6、β-微精浆蛋白基因和染色体8q24区与前列腺癌的关联研究

目的 探讨整合素α6(ITGA6)基因(rs12621278,G)、染色体8q24区(rs10086908,T)和β-微精浆蛋白(MSMB)基因(rs10993994,T)与北京市居民中前列腺癌(PCa)的关联,了解PCa患者基因型和表型的关系.方法 收集112例PCa患者临床、遗传、膳食习惯、嗜好等表型,对PCa患者和91名正常对照者的ITGA6基因(rs12621278,G)、染色体8q24区(rs10086908,T)和MSMB基因(rs10993994,T)进行比较,并进行病例组的基因型-表型分析.结果 2组间相比,MSMB基因rs10993994,T风险等位基因频率差异有统计学意义(病例组56.4%,对照组46.2%;P=0.001,OR=1.97,95%CI为1.28～3.04).8q24区的rs10086908,T(病例组83.5%,对照组79.2%)和ITGA6基因的rs12621278,G(病例组27.2%,对照组27.0%)组间差异无统计学意义(P＞0.05).数量性状分析发现ITGA6风险基因型(G/G)的患者病程为(1.40±0.55)年,显著短于A/G型的(4.38±3.10)年和A/A型的(2.37±1.84)年(P=0.003).结论 MSMB基因变异和PCa易感性之间存在相关性,提示MSMB基因可能与PCa有关联.

Abstract：

Objective To explore the correlation between ITGA6 gene (rs12621278, G), MSMB gene (rs10993994, T), chromosome 8q24 (rs10086908, T) and prostate cancer (PCa) in Beijing residents, and to explore the correlation between genotype and phenotype in PCa patients. Methods PCa patient phenotypes were collected including clinical, genetic, dietary habits, hobbies and blood samples. ITGA6 gene (rs12621278, G), chromosome 8q24 (rs10086908, T) and MSMB gene (rs10993994, T) compared the allele distribution between 112 PCa and 91 healthy control age matched patients. The genotype and phenotype analysis was conducted in the 2 groups. Results Between the case and control groups, only rs10993994, T of MSMB gene (case 56.4%,control 46.2%) was significantly different (P=0.001; OR=1.97, 95%CI:1.28-3.04). The rs10086908, T of 8q24 (case 83.5%, control 79.2%) and rs12621278, G of ITGA6 gene (case 27.2%, control 27.0%) were not significantly associated with PCa in the study sample (P>0.05). Quantitative trait analysis showed that the disease duration of ITGA6 risk genotypes (G/G,1.40±0.55 years) in PCa patients was significantly shorter (P=0.003) than the other genotype carriers (A/G, 4.38±3.10 years; A/A, 2.37±1.84 years). Conclusion The genetic variation in MSMB is possibly associated with PCa susceptibility, suggesting that MSMB genes might be associated with PCa in a Chinese population.     

Association of gene variants with susceptibility to type 2 diabetes among Omanis

AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped,by an allelic discrimination assay-by-design TaqMan method on fast real time polymerase chain reaction system,for the following gene variants:KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398),CDKN2A/B(rs10811661),FTO(rs9939609 and rs8050136),IGF2BP2(rs4402960),SLC30A8(rs13266634)CAPN10(rs3792267)and HHEX(rs1111875).T2D patients were recruited from the Diabetes Clinic(n=243)and inpatients(n=749)at Sultan Qaboos Univesity Hospital(SQUH),Muscat,Oman.Adult control participants(n=294)were volunteers from the community and from those visiting Family Medicine Clinic at SQU,for regular medical checkup.The difficulty in recruiting Omani participants with no family history of diabetes was the main reason behind the small number of control participants in this study.Almost all volunteers questioned had a relativewith diabetes mellitus.Inspite of the small number of normoglycemic controls in this study,this sample was sufficient for detection of genes and loci for common alleles influencing T2D with an odds ratio of≥1.3reaching at least 80%power.Data was collected from June 2010 to February 2012.RESULTS:Using binary logistic regression analysis,four gene variants showed significant association with T2D risk:KCNJ11(rs5219,P=5.8×10~(-6),OR=1.74),TCF7L2(rs7903146,P=0.001,OR=1.46),CDKAL1(rs10946398,P=0.002,OR=1.44)and CDKN2A/B(rs10811661,P=0.020,OR=1.40).The fixation index analysis of these four gene variants indicated significant genetic differentiation between diabetics and controls{[KCNJ11(rs5219),P0.001],[TCF7L2(rs7903146),P0.001],[CDKAL1(rs10946398),P0.05],[CDKN2A/B(rs10811661),P0.05]}.The highest genotype variation%between diabetics and controls was found at KCNJ11(2.07%)and TCF7L2(1.62%).This study was not able to detect an association of T2D risk with gene variants of IGF2BP2(rs4402960),SLC30A8(rs13266634),CAPN10(rs3792267)and HHEX(rs1111875).Moreover,no association was found between FTO gene variants(rs9939609 and rs8050136)and T2D risk.However,T2D risk was found to be significantly associated with obesity(P=0.002,OR=2.22);and with the Waist-to-Hip ratio(n=532,P=1.9×10~(-7),OR=2.4),[among males(n=234,P=1.2×10~(-4),OR=2.0)and females(n=298,P=0.001,OR=6.3)].CONCLUSION:Results confirmed the association of KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398)and CDKN2A/B(rs10811661)gene variants with susceptibility to T2D among Omani Arabs.     

丙泊酚对大鼠机械通气相关肺损伤的保护作用及机制

Objective To investigate the mechanisms of propofol on ventilator-induced lung injury in rats produced by high PIP ventilation. Methods Twenty-four anesthetized Wistar rats weighting 280 g-320 g were randomly divided into tlhree groups (n=8). Rats were ventilated with high PIP pattern (PIP=25 cm H2O,PEEP=2 cm H2O) for 4 h. Propofol was given in a bolus of 2 mg/kg (group B) or 5 mg/kg (group C), followed by continuous infusion with 4 mg·kg-1·h-1 (group B)or 10 mg·kg-1·h-1(group C). No Propofol was given for group A. MAP, HR were recorded and arterial blood gases were analyzed. Lung wet and dry weight ratio( W/D), tumor necrosis factora(TNF-α), interleukin1β(IL-1β), IL-6, IL-10, macrophage inflammatory protein2(MIP-2) and protein content in bronchoalveolar lavage fluid (BALF) , content of malondialdehyde (MDA) and superoxide dismutase (SOD) in lung homogenate were determined.Pathological change of lung was examined and lung injury was scored as well. Results MAP and PaO2 decreased from (116±7.4) mm Hg and (379±65) mm Hg to (73±21 )mm Hg and (103±48)mm Hg, and PaCO2 increased at fourth hour in group A(P<0.05). PaO2 in group B and C were higher than in group A after 3 h(P<0.05). Lung W/D weight ratio, TNF-α, MIP-2 and protein content in BALF were higher in group A (P<0.05), and MDA was higher in group A (P<0.05). No significant difference between group B and C. Pathological changes of lung in group B and C were all better than those in group A. Conclusion Propofol may attenuate VILI in rats partly by reducing the release of cytokine, decreasing the accumulation of neutrophil in the lung, and inhibiting peroxidized injury.     

Benefits of the use of blood conservation in scoliosis surgery

AIM To investigate whether autologous blood transfusion(ABT) drains and intra-operative cell salvage reduced donor blood transfusion requirements during scoliosis surgery.METHODS Retrospective data collection on transfusion requirements of patients undergoing scoliosis surgery is between January 2006 and March 2010. There were three distinct phases of transfusion practice over this time: Group A received "traditional treatment" with allogeneic red cell transfusion(ARCT) in response to an intra- or postoperative anaemia(Hb 8 g/d L or a symptomatic anaemia); Group B received intra-operative cell salvage in addition to "traditional treatment". In group C,ABT wound drains were used together with both intra-operative cell salvage and "traditional treatment".RESULTS Data from 97 procedures on 77 patients,there was no difference in mean preoperative haemoglobin levels between the groups(A: 13.1 g/d L; B: 13.49 g/d L; C: 13.66 g/d L). Allogeneic red cell transfusion was required for 22 of the 37 procedures(59%) in group A,17 of 30(57%) in group B and 16 of 30(53%) in group C. There was an overall 6% reduction in the proportion of patients requiring an ARCT between groups A and C but this was not statistically significant(χ2 = 0.398). Patientsin group C received fewer units(mean 2.19) than group B(mean 2.94)(P = 0.984) and significantly fewer than those in group A(mean 3.82)(P = 0.0322). Mean length of inpatient stay was lower in group C(8.65 d) than in groups B(12.83) or A(12.62).CONCLUSION When used alongside measures to minimise blood loss during surgery,ABT drains and intra-operative cell salvage leads to a reduced need for donor blood transfusion in patients undergoing scoliosis surgery.     

多沙唑嗪对兔膀胱出口部分梗阻致膀胱顺应性减低的影响

目的 探讨多沙唑嗪对兔膀胱出口部分梗阻后膀胱顺应性改变的影响.方法 成年雄性新西兰兔40只随机分为4组,每组10只,A组为假手术对照组,B组为膀胱出口部分梗阻组,C组为膀胱出口部分梗阻后口服多沙唑嗪组,D组为假手术后给予多沙唑嗪组.各组于14周行尿动力学检测,检测完成后处死并留取膀胱标本,行膀胱称重.结果 4组膀胱标本质量分别为(3.2±0.9)、(14.1±2.3)、(5.0±2.0)、(2.9±0.5)g;B、C组均高于A、D组,B组高于C组,差异均有统计学意义(P＜0.01);A、D组间比较差异无统计学意义(P＞0.05).4组逼尿肌漏尿点压分别为(10.2±2.5)、(18.8±6.1)、(13.5±4.7)、(11.6±3.6)cm H2O(1 cm H2O=0.098 kPa),B组高于A、D组,差异有统计学意义(P＜0.01),且高于C组,差异有统计学意义(P＜0.05);A、C、D组间差异无统计学意义(P＞0.05).膀胱顺应性分别为(2.86±0.56)、(1.22±0.39)、(4.25±2.19)、(2.90±0.53)ml/cm H2O,B组与A、D组相比明显下降,差异有统计学意义(P＜0.01);C组高于A、D组,差异有统计学意义(P＜0.05);A、D组间差异无统计学意义(P＞0.05).结论膀胱出口部分梗阻后早期应用多沙唑嗪治疗能够延迟梗阻对膀胱顺应性的损害,保护膀胱储尿功能.

Abstract：

Objective To explore the effect of doxazosin on rabbit bladder compliance after partial bladder outlet obstruction. Methods A total of 40 male New Zealand white rabbits were randomized into 4 groups, with 10 rabbits in each group. Partial bladder outlet obstruction was established in groups B and C, while groups A and D underwent the same operation but without partial bladder outlet obstruction. On the day after the operation, groups C and D received oral administration of doxazosin. After 14 weeks, urodynamic examinations were carried out in all groups, and the bladder was weighted after cystectomy. Results Bladder weight was (3.2±0.9) g in group A, (14.1±2.3) g in group B, (5.0±2.0) in group C,and (2.9±0.5) g in group D. The bladder weight in groups B and C increased significantly compared to groups A and D (P＜0.01), group B increased significantly over group C (P＜0.01), and there was no significant difference between groups A and D (P＞0.05).The detrusor leak point pressure was (10.2±2.5) cm H2O in group A, (18.8±6.1) cm H2O in group B, (13.5±4.7) cm H2O in group C,and (11.6±3.6) cm H2O in group D. The detrusor leak point pressure in group B was significantly higher than group A, group D (P＜0.01) and group C (P＜0.05). There was no significant difference between group A, group C and group D (P＞0.05). The bladder compliance was (2.86±0.56) ml/cm H2O in group A, (1.22±0.39) ml/cm H2O in group B, (4.25±2.19) ml/cm H2O in group C,and (2.90±0.53) ml/cm H2O in group D. The bladder compliance was significantly decreased in group B compared to groups A and D (P＜0.01). Bladder compliance in group C was significantly higher than in groups A and D (P＜0.05), and there was no significant difference between group A and group D (P＞0.05). Conclusion Early use of doxazosin can delay the occurrence of lower bladder compliance after partial bladder outlet obstruction, thus protecting the storage function of bladder.     

肾移植一年后急性排斥反应时移植肾组织中C4d表达阳性的临床研究

Objective To analyze C4d deposition in the patients with late acute renal allograft rejection,and explore the role of C4d in grafts survival and grafts loss. Methods Thirty-six patients clinical and pathologically diagnosed as having acute rejection more than one year post-transplant were selected. C4d was detected by immunohistochemistry in renal allograft biopsies. The effect of C4d deposition on long-term graft survival was studied. Results Among 36 recipients with late acute renal allograft rejection, 16 cases were positive for C4d (44.4 %) and 20 negative for C4d (55.6 %). Five cases experienced graft loss in C4d positive group (31.3 %), while 6 cases in C4d negative group (30.0%). There was no significant difference in the graft loss rate between C4d-positive group and C4d-negative group. Log-Rank test demonstrated there was no significant difference in graft survival between C4d-positive group and C4d-negative group. The count of the interstitial infiltrated eosinophils in renal allograft was (9.4 + 4.5) and (2.6 + 1.8) respectively in the C4d-positive group and C4dnegative group (P＜0.05). Conclusion C4d deposition in peritubular capillary of the recipients with late acute renal allograft rejection might not be a prognostic marker for graft outcome.     

Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

The precise aetiology of benign prostatic hyperplasia （BPH） remains unclear; however, it is known that immunological inflammatory processes have a role in the pathogenesis of BPH initiation and progression. Nitric oxide synthase 2 （NOS2） inducible expression is closely correlated with prostatic disease, including prostate cancer and BPH. The aim of this study was to investigate the relationship between NOS2 polymorphisms and BPH. With a cohort of 205 controls and 229 BPH subjects, we genotyped three single nucleotide polymorphisms （SNPs） in the NOS2 gene, including rs2779248 （promoter, -278 T/C）, rs 10459953 （5＇-untranslated region） and rs2297518 （exon 16, missense, Ser608Leu）, using direct sequencing and restriction fragment length polymorphism. The genotypic and allelic frequencies between control and BPH subjects were compared, and the associations among the BPH subjects were analyzed. SNPStats, SNPAnalyzer and HelixTree programmes were used to analyze SNPs. There was no association on SNPs between control and BPH subjects. When BPH subjects were analyzed, there was no association on SNPs between the low and high prostate-specific antigen groups. However, one SNP （rs 10459953, odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.29-0.65, P 〈 0.0001, in codominant model; OR = 0.23, 95% CI = 0.12-0.46, P 〈 0.0001, in dominant model; and OR = 0.46, 95% CI = 0.24-0.86, P = 0.015, in recessive model） was associated with prostatic volume in BPH. We detected a strong association in genotype frequencies of NOS2 SNP （rs10459953） between subjects with small and large prostatic volume in BPH. The result suggests that NOS2 may be associated with prostatic volume in BPH.     

他克莫司胶囊和缓释胶囊预防肝移植急性排斥反应的效果和安全性

Objective To evaluate the efficacy and safety of tacrolimus exposure in stable liver transplant recipients converted from FK506 twice a day to Advagraf (tacrolimus extended-release capsules) once daily. Methods This was an open-label, random, control and multi-center study.Eligible patients were 19 to 70 years of age, 6 months post-transplant with stable renal and hepatic function and receiving stable doses of tacrolimus twice a day for 2 weeks prior to enrollment. There were 86 patients in the experimental group and the control group, separately. The average age of experimental group and control group was 46 ± 10 and 49 ± 9, respectively. Patients in experimental group received Advagraf, once daily, and the dose was adjusted according to the drug concentration,and the drug concentration was between 2 to 10 μg/L. The control group given tacrolimus, twice daily, and the drug concentration was between 2 to 10 μg/L. Results The incidence of acute rejection reaction was 1.20 % and 1.18 % respectively in experimental group and control group, and the 95 %confidence interval was -3.25% ～3.31 % and -3.26% ～ 3.34 %, individually. There was 1 case of acute rejection reaction in experimental group and control group, respectively. The patient and organ survival rate was 100%. Sixteen adverse events occurred in 15 patients (17.65 %) of the experimental group, and 10 adverse events occurred in 10 patients (11.63 %) of control group. Severe adverse events relating to the test drug in experimental group occurred in 4 patients (4. 71 %). and 2 patients (2. 33) in control group.Conclision Clinical trials indicated that Advagraf has efficacy and safety profiles similar to those of tacrolimus. The drug is safe and may improve patient compliance.     

他克莫司胶囊和缓释胶囊预防肝移植急性排斥反应的效果和安全性

Objective To evaluate the efficacy and safety of tacrolimus exposure in stable liver transplant recipients converted from FK506 twice a day to Advagraf (tacrolimus extended-release capsules) once daily. Methods This was an open-label, random, control and multi-center study.Eligible patients were 19 to 70 years of age, 6 months post-transplant with stable renal and hepatic function and receiving stable doses of tacrolimus twice a day for 2 weeks prior to enrollment. There were 86 patients in the experimental group and the control group, separately. The average age of experimental group and control group was 46 ± 10 and 49 ± 9, respectively. Patients in experimental group received Advagraf, once daily, and the dose was adjusted according to the drug concentration,and the drug concentration was between 2 to 10 μg/L. The control group given tacrolimus, twice daily, and the drug concentration was between 2 to 10 μg/L. Results The incidence of acute rejection reaction was 1.20 % and 1.18 % respectively in experimental group and control group, and the 95 %confidence interval was -3.25% ～3.31 % and -3.26% ～ 3.34 %, individually. There was 1 case of acute rejection reaction in experimental group and control group, respectively. The patient and organ survival rate was 100%. Sixteen adverse events occurred in 15 patients (17.65 %) of the experimental group, and 10 adverse events occurred in 10 patients (11.63 %) of control group. Severe adverse events relating to the test drug in experimental group occurred in 4 patients (4. 71 %). and 2 patients (2. 33) in control group.Conclision Clinical trials indicated that Advagraf has efficacy and safety profiles similar to those of tacrolimus. The drug is safe and may improve patient compliance.     

他克莫司胶囊和缓释胶囊预防肝移植急性排斥反应的效果和安全性

Objective To evaluate the efficacy and safety of tacrolimus exposure in stable liver transplant recipients converted from FK506 twice a day to Advagraf (tacrolimus extended-release capsules) once daily. Methods This was an open-label, random, control and multi-center study.Eligible patients were 19 to 70 years of age, 6 months post-transplant with stable renal and hepatic function and receiving stable doses of tacrolimus twice a day for 2 weeks prior to enrollment. There were 86 patients in the experimental group and the control group, separately. The average age of experimental group and control group was 46 ± 10 and 49 ± 9, respectively. Patients in experimental group received Advagraf, once daily, and the dose was adjusted according to the drug concentration,and the drug concentration was between 2 to 10 μg/L. The control group given tacrolimus, twice daily, and the drug concentration was between 2 to 10 μg/L. Results The incidence of acute rejection reaction was 1.20 % and 1.18 % respectively in experimental group and control group, and the 95 %confidence interval was -3.25% ～3.31 % and -3.26% ～ 3.34 %, individually. There was 1 case of acute rejection reaction in experimental group and control group, respectively. The patient and organ survival rate was 100%. Sixteen adverse events occurred in 15 patients (17.65 %) of the experimental group, and 10 adverse events occurred in 10 patients (11.63 %) of control group. Severe adverse events relating to the test drug in experimental group occurred in 4 patients (4. 71 %). and 2 patients (2. 33) in control group.Conclision Clinical trials indicated that Advagraf has efficacy and safety profiles similar to those of tacrolimus. The drug is safe and may improve patient compliance.     

中国北方人群维生素D受体基因多态性与腰椎退变性椎间盘疾病关联研究

背景：退变性椎间盘疾病（degenerative disc disease,DDD）的发生由机体内在基因和外在环境因素综合作用导致,维生素D受体（vitaminDreceptor,VDR）基因可能同腰椎DDD的发生存在相关性。 目的：探讨VDR基因多态性与腰椎DDD发生的关系。 方法：采用病例对照研究方法,以MRI确诊腰椎间盘退变患者118例为病例组,无腰椎间盘退变者112例为对照。应用VeraCode GoldenGate Genotyping Assay SNPs检测系统检测VDR基因的单核苷酸多态性（single nucleotide polymorphism,SNP）信息,分析两组VDR基因多态性的差异。 结果：筛查VDR基因16个位点,rs2239179等位基因在病例组和对照组中的分布频率存在差异（P=0．046）,经Permutation校正后差异无统计学意义（P=0．4299）,其他各位点等位基因在病例组和对照组中的分布频率差异均无统计学意义（P值均〉0．05）。VDR基因各位点基因型在病例组和对照组中的分布频率差异均无统计学意义（P值均〉0．05）。在非条件Logistic回归分析中,未发现VDR基因各位点符合Codominant、Dominant、Recessive、Overdominant或Log-additive遗传模型。在VDR基因的各单倍体型中,病例组和对照组间的频率分布差异均无统计学意义（P值均〉0．05）。 VDR基因多态性与腰椎DDD的发生可能无关。     

Association of catechol-O-methyltransferase genetic variants with outcome in patients undergoing surgical treatment for lumbar degenerative disc disease

Background context

Surgical treatment for lumbar degenerative disc disease (DDD) has been associated with highly variable results in terms of postoperative pain relief and functional improvement. Many experts believe that DDD should be considered a chronic pain disorder as opposed to a degenerative disease. Genetic variation of the catechol-O-methyltransferase (COMT) gene has been associated with variation in human pain sensitivity and response to analgesics in previous studies.

Purpose

To determine whether genetic variation of COMT is associated with clinical outcome after surgical treatment for DDD.

Study design

Prospective genetic association study.

Patient sample

Sixty-nine patients undergoing surgical treatment for lumbar DDD. Diagnosis was based on documentation of chronic disabling low back pain (LBP) present for a minimum of 6 months and unresponsive to supervised nonoperative treatment, including activity modification, medication, physical therapy, and/or injection therapy. Plain radiographs and magnetic resonance imaging revealed intervertebral disc desiccation, tears, and/or collapse without focal herniation, nerve root compression, stenosis, spondylolisthesis, spondylolysis, or alternative diagnoses.

Outcome measures

Oswestry Disability Index (ODI) and visual analog score (VAS) for LBP.

Methods

Surgical treatment included 65 instrumented fusions and four disc arthroplasty procedures. All patients completed preoperative and 1-year postoperative ODI questionnaires. DNA was extracted from a sample of venous blood, and genotype analysis was performed for five common COMT single nucleotide polymorphisms (SNPs). Potential genetic association between these COMT SNPs and the primary outcome variable, 1-year change in ODI, was investigated using both single-marker and haplotype association analyses. Association with VAS scores for LBP was analyzed as a secondary outcome variable.

Results

Single-marker analysis revealed that the COMT SNP rs4633 was significantly associated with greater improvement in ODI score 1 year after surgery (p=.03), with individuals homozygous for the less common “T” allele demonstrating the largest improvement in ODI. Haplotype analysis of four COMT SNPs, rs6269, rs4633, rs4818, and rs4680, also identified a common haplotype “ATCA” (haplotype frequency of 39.3% in the study population) associated with greater improvement in ODI (p=.046). The greatest mean improvement in ODI was observed in patients homozygous for the “ATCA” COMT haplotype. A nonsignificant trend was observed between SNP rs4633 and greater improvement in VAS score for LBP.

Conclusions

This is the first study to report an association between surgical treatment success in DDD patients and genetic variation in the putative pain sensitivity gene COMT. These findings require replication in other DDD populations but suggest that genetic testing for pain-relevant genetic markers such as COMT may provide useful clinical information in terms of predicting outcome after surgery for patients diagnosed with DDD.     

桂西地区中老年人脂联素基因多态性与骨质疏松症的相关性

目的 探讨桂西地区中老年人脂联素基因多态性与骨质疏松症的相关性。方法 选取桂西地区中老年人志愿者623名,进行超声骨密度测量、脂联素基因多态性位点分析及SNPs位点的连锁不平衡分析。结果 同年龄（55岁以上）男性骨量值高于女性（P＜0.05）,骨量正常的个体比例随年龄的增长而下降,而骨质疏松症的患病率则随年龄增长而增加。脂联素基因5个SNPs位点均达到Hardy-Weinberg平衡（P＞0.05）,其中SNP位点rs1063539的CG基因型在骨质疏松病例组分布高于正常组,而GG基因型在病例组中的分布则低于正常组。CG型可能是骨密度的一个保护基因型,等位基因C可能与骨质疏松症的发生呈负相关。SNP位点rs3774261的AA基因型在病例组中的分布高于正常组。连锁不平衡检测发现,脂联素基因的5个SNP位点之间不存在连锁关系。结论 脂联素基因的SNP位点rs1063539和rs3774261与桂西地区中老年人群的骨质疏松有密切关系。     

The involvement of ADAMTS‐5 genetic polymorphisms in predisposition and diffusion tensor imaging alterations of lumbar disc degeneration

Purpose: Low back pain is a global health problem in which more than 40% is caused by lumbar intervertebral disc degeneration (LDD). ADAMTS‐5 (A disintegrin and metalloproteinase with thrombospondin motifs‐5) was shown to be involved in LDD by functional analyses. To identify whether there is an association between ADAMTS‐5 and LDD, and what is the contribution of ADAMTS‐5 genetic polymorphisms to MD (Mean diffusivity) changes in lumbar IVD (Intervertebral disc). We firstly genotyped selected ADAMTS‐5 SNPs (Single nucleotide polymorphisms) in a Chinese Han population. After the primary analyses of allelic, genotypic, and haplotypic association, we performed SNP–SNP interaction analysis. We subsequently genotyped another 50 participants and acquired the corresponding MD values from individual lumbar IVDs. The association analysis between the genotypic groups divided by the above positive SNPs and the corresponding MD values were also performed. Significant associations were identified in rs151058, rs229052, and rs162502. None of the 2‐SNP haplotypic analysis survived the 10,000 permutation test. The following interaction analysis demonstrated that rs151058 was strong associated with LDD when conditioning on rs162502. Significant difference of MD values between AA and G+ carriers was identified in rs162502. This is the first study indicating that the SNPs of ADAMTS‐5 may contribute to predisposition of LDD. An interaction between rs151058 and rs229052 may exist in ADAMTS‐5 with LDD. The rs162502 might be associated with altered MD values. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:686–694, 2014.     

Association of COL2A1 Gene Polymorphism with Degenerative Lumbar Scoliosis

Background

Degenerative lumbar scoliosis (DLS) progresses with aging after 50-60 years, and the genetic association of DLS remains largely unclear. In this study, the genetic association between collagen type II alpha 1 (COL2A1) gene and DLS was investigated.

Methods

COL2A1 gene polymorphism was investigated in DLS subjects compared to healthy controls to investigate the possibility of its association with COL2A1 gene. Based on a single nucleotide polymorphism (SNP) database, SNP (rs2276454) in COL2A1 were selected and genotyped using direct sequencing in 51 patients with DLS and 235 healthy controls. The SNP effects were analyzed using three models of codominant, dominant, and recessive. Logistic regression models were calculated for odds ratios (ORs) with 95% confidence intervals (CIs) and corresponding p-values, controlling age and gender as co-variables.

Results

SNP (rs2276454) in COL2A1 was significantly associated with the degenerative lumbar scoliosis in the codominant (OR, 1.90; 95% CI, 1.17 to 3.10; p = 0.008) and dominant models (OR, 3.58; 95% CI, 1.59 to 9.29; p = 0.001).

Conclusions

The results suggest that COL2A1 is associated with the risk of DLS in Korean population.     

膝骨关节炎与相关金属蛋白酶的基因多态性关联研究

目的探讨带有血小板凝血酶敏感蛋白样模体的解整链蛋白金属蛋白酶5(ADAMTS-5)基因单核苷酸多态性(SNP)与膝骨关节炎的关联性。 方法连续收集洛阳正骨医院188例膝骨关节炎患者作为病例组，对照组收集排除疾病诊断的100人。应用基因组变异服务器(GVS)网站选择ADAMTS-5基因共计15个SNP位点，采用基质辅助激光解析飞行时间质谱分析技术(MALDI-TOF-MS)进行SNP分型，先行哈迪温伯格(HW)平衡检测，对符合HW平衡的SNP位点等位基因进行卡方检验及单体型分析，对基因型进行logistic回归分析。 结果病例组rs2249350位点C等位基因显著多于对照组[比值比(OR)＝1.176，95%置信区间(CI)(1.025，1.351)，P＝0.016]，A等位基因显著少于对照组[OR＝0.761，95%CI(0.612，0.947)，P＝0.016]；rs2249350位点AA基因型[OR＝0.288，95%CI(0.124，0.669)，P＝0.004]及隐性基因模型[OR＝0.348，95%CI(0.162，0.749)，P＝0.007]均与膝关节骨关节炎负相关；rs229054、rs2249350两位点存在连锁不平衡，构成GC、GA、AC共3个单体型区块，其中病例组单体型GC显著多于对照组[OR＝1.259，95%CI(1.032，1.537)，P＝0.019]，而GA则显著少于对照组[OR＝0.763，95%CI(0.614，0.949)，P＝0.017]。 结论ADAMTS-5基因rs2249350位点C等位基因可能是膝关节骨关节炎的致病性因素，A等位基因则可能是保护性因素；rs2249350位点AA基因型可能是膝关节骨关节炎的保护性基因型，降低患病风险，且A等位基因可能为隐性基因，隐性遗传；rs229054、rs2249350位点GC单体型可能是膝关节骨关节炎的致病性因素，而GA单体型则可能是保护性因素。该位点等位基因、基因型及单体型与膝关节骨关节炎的关系仍需进一步深入研究和验证。     

24个单核苷酸多态性位点与皖北地区布加综合征相关性研究

目的探讨24个相关基因单核苷酸多态性(SNPs)位点与皖北地区布加综合征(BCS)的关系,为BCS的诊断和针对性治疗提供新依据。方法选取2017年2月至2019年6月蚌埠医学院第一附属医院收治的80例BCS患者(BCS组),另选取同期80例健康体检者(对照组),静脉血提取DNA,应用Agena MassARRAY SNP结合多重PCR技术、MassARRAY iPLEX单碱基延伸技术和基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术通过检测延伸产物相对分子量对21个基因中24个SNPs进行分型检测,分析各基因型、等位基因的差异表达。结果其中6个SNPs位点统计结果不符合Hardy-Weinberg平衡;18个SNPs位点基因型频率分布在BCS组及对照组间差异无统计学意义。BCS组MTHFR C677T(rs1801133)基因位点A等位基因频率高于对照组(OR=2.769,95%CI:1.171~4.465,P=0.004)。结论MTHFR C677T(rs1801133)基因位点A等位基因可能是皖北地区BCS的危险因素。     

雌激素受体β的单核苷酸多态性与前列腺癌风险的相关性研究

目的研究雌激素受体β(ERβ)的单核苷酸多态性(SNPs)与前列腺癌(CaP)风险的相关性。方法对40例CaP患者和86例正常对照者利用直接测序法对ERβ基因中的4个SNPs(近端启动子上游的3个SNPsrs3829768,rs1271572,rs3841304和外显子7上的SNPsrs1256049)进行基因分型,分析单个位点的等位基因和基因频率是否与CaP相关。结果由于不符合HardyWeinberg平衡,SNP位点rs3841304被排除。发现在CaP患者中,近端启动子上游的SNPs位点rs3829768(A/G)的G和rs1271572(C/A)的A等位基因频率及其基因型频率均显著低于正常对照者(P<0.01)。结论ERβ基因近端启动子上游有2个SNPs与汉族CaP之间存在显著的相关性。     

Association analysis of single nucleotide polymorphisms in cartilage-specific collagen genes with knee and hip osteoarthritis in the Japanese population.

Osteoarthritis (OA) is one of the most common diseases in the elderly. Although its pathophysiology is complex and its molecular basis remains to be determined, much evidence suggests that OA has strong genetic determinants. To search for susceptibility loci of OA, we selected seven candidate genes encoding cartilage-specific collagens (type II, IX, X, and XI collagens) and performed association analysis for OA using single nucleotide polymorphisms (SNPs) in the coding region of these genes. Four hundred seventeen OA samples and 280 control samples were collected from the Japanese population, and 12 SNPs were genotyped. Our studies have identified two susceptibility loci of OA: COL2A1 and COL9A3. An SNP in COL9A3 showed significant association with knee OA (p = 0.002, odds ratio [OR] = 1.48). Haplotype analysis showed significant association between a specific haplotype of COL2A1 and hip OA (p = 0.024; OR = 1.30). Further analysis of these two genes will shed light on the molecular mechanisms of OA.     

Degenerated intervertebral disc prolapse and its association of collagen I alpha 1 Spl gene polymorphism: A preliminary case control study of Indian population

Background:

Degenerated disc disease (DDD) is a common disorder responsible for increased morbidity in a productive age group. Its etiology is multifactorial and genetic factors have been predominantly implicated. Disc prolapse results due to tear in the annulus, which is a fibrous structure composed largely of type I collagen. Functional polymorphism at the Sp1 site of the collagen I alpha 1 (COL1A1) gene has shown a positive association with DDD in Dutch and Greek populations. The purpose of this study was to assess COL1A1 Sp1 gene polymorphism in the Indian population.

Materials and Methods:

Fifty clinically and radiologically proven patients with disc prolapse requiring surgery were included as cases and 50 healthy, age-matched volunteers served as controls. After isolating DNA from their blood sample, genotyping for COL1A1 polymorphism (rs1800012) was performed and identified as GG, GT, and TT.

Results:

The mean age and body mass index in cases and controls were similar. 76% of the patients were males. The most common site of disc degeneration was L4–L5 (36%), followed by L5–S1 (34%). Homozygous–GG, heterozygous GT, and homozygous TT genotypes were seen in 38 (76%), 10 (20%) and 2 (4%) cases respectively, controls had similar percentage of genotypes as well. The alleles in cases and the control group showed no significant difference (P = 0.6744) and followed the Hardy–Weinberg Equilibrium in the study population.

Conclusion:

The COL1A1 (rs1800012) is in Hardy–Weinberg equilibrium in the present subset of Indian population. But taken as a single factor, it was not found to be associated with DDD in this preliminary study. Disc degeneration is multifactorial and also anticipated to be a result of multiple genes involvement and gene-gene interaction.