护骨素基因T950C及A163G多态性与老年2型糖尿病患者的骨密度

背景：2型糖尿病患者发生骨质疏松症的比率较高。 目的：观察老年2型糖尿病患者护骨素基因启动子区域T950C、A163G位点多态性与骨密度的关系。 方法：纳入147例老年2型糖尿病患者,男性100例,女性47例,应用多聚酶链反应-限制性片段长度多态性方法测定患者护骨素基因T950C、A163G的基因型;采用双能X线骨密度吸收仪测定患者腰椎、髋部及前臂的骨密度。 结果与结论：在老年女性2型糖尿病患者中,T950C不同基因型在特定部位具不同骨密度,CC基因型的腰椎L2、L4骨密度高于TC或TT型;在老年男性2型糖尿病患者中,未发现T950C不同基因型与骨密度相关。在老年女性2型糖尿病患者中,A163G不同基因型在特定部位具不同骨密度,AA型的股骨大转子、前臂骨密度高于AG或GG型;在老年男性2型糖尿病患者中AA型的腰椎L3、L4骨密度高于AG或GG型。表明护骨素基因启动子区T950C基因多态性与老年女性2型糖尿病患者的骨密度相关,A163G基因多态性与老年男、女性2型糖尿病患者的骨密度皆相关。     

护骨素基因T245G多态性与老年人骨密度关系的部位及性别差异*☆

背景：作为骨折发生的重要临床预测因子,骨密度在一定程度上由遗传因素决定。护骨素基因是骨质疏松症发病中的重要候选基因。 目的：探讨护骨素基因T245G多态性与骨密度的相关性。 方法：选取2008-09/2010-04在北京大学人民医院进行常规查体的老年人281名,其中男182名,女99名。应用PCR-RFLP结合DNA测序检测护骨素基因T245G多态性,使用双能X射线骨密度测量仪测定受试者腰椎、髋部标准位置及前臂的骨密度。同时收集受试者的生化指标及临床观察项目。应用ANOVA方法分析护骨素基因T245G多态性与各检测指标的关系。 结果与结论：在老年男性及绝经后女性中,T245G基因T,G等位基因频率分布差异无显著性意义(P > 0.05)。在老年男性中,GG和TG基因型具有较高的腰椎骨密度,而TT基因型的腰椎骨密度较低(P < 0.05),Ward’s三角区及前臂骨密度在各基因型间差异无显著性意义(P > 0.05)。在绝经后女性中,T245G多态性与骨密度无关,说明护骨素基因与老年男性腰椎骨密度有关。     

降钙素受体基因多态性与原发性骨质疏松的相关性★

目的：骨质疏松是多基因调控疾病，峰值骨量达到和骨量丢失均受遗传因素影响。观察山东半岛地区汉族人群降钙素受体Alu-Ⅰ基因多态性各基因型频率及其与骨质疏松的关系，探讨原发性骨质疏松症的遗传易感因素。 方法：试验于2005-06/2007-06在青岛大学医学院附属医院中心实验室完成。①试验对象：选取332名长期居住在山东半岛地区无亲缘关系的汉族人群，纳入标准：健康门诊查体人员、原发性骨质疏松症及原发性骨质疏松症所致骨折患者；患者对试验知情同意。排除标准：各种继发性骨质疏松症；影响骨代谢相关疾病史；服用影响骨代谢药物等。其中骨质疏松合并骨折75例作为骨质疏松性骨折组，余257例经过骨密度测定确定骨量，按骨质疏松诊断标准（骨密度测定值比同性别峰值骨密度均值降低2.5个标准差）分为骨量正常组（n =201）及骨质疏松组（n =56）。②试验方法：应用聚合酶链反应限制性片段长度多态性分析技术测定257名山东半岛汉族成年人和75名骨质疏松性骨折患者降钙素受体基因型，用双能X射线吸收法测定腰椎、股骨颈、粗隆间、Ward’s三角和大转子区等部位的骨密度值。 结果：纳入受试者332人，均进入结果分析。①本试验人群降钙素受体基因型频率分布均符合Hardy-Weinberg 定律(χ2=0.47，P =0.493)。基因型频率分布依次为CC型占89.5%，CT型占10.5%，TT型占0%。②年龄与不同部位骨密度值之间呈负相关（P < 0.01），体质量指数与骨密度值之间呈正相关（P < 0.01），在将年龄和体质量指数进行校正后发现女性CC基因型较CT基因型在ward’s三角区有较高的骨密度（P < 0.05)，骨量正常组各基因型与骨质疏松性骨折组之间差异无显著性意义（P > 0.05)。 结论：山东半岛汉族女性降钙素受体基因型与骨密度之间存在一定关联，降钙素受体C1377T基因多态性可能成为胶东半岛汉族女性发生骨质疏松危险性的遗传标志。     

维生素D受体基因多个位点多态性与绝经后妇女骨密度及骨转换生化标志物的关系

目的：观察维生素D受体基因BSMⅠ,TAQⅠ,APAⅠ多态性与绝经后妇女骨密度及骨转换生化标志物的相关性。 方法：①2007-01/2008-12从福州常住汉族人中随机检测绝经后妇女576例, 年龄48-84(62.17±6.37)岁。受试者均知情同意。②记录年龄、绝经年限、体质量指数和绝经后骨折情况。③双能X射线骨密度仪检测正位第2~4腰椎、左侧股骨颈、大转子和Ward s三角区骨密度。④PCR-RFLP技术检测维生素D受体基因BSMⅠ,TAQⅠ,APAⅠ多态性。⑤用酶联免疫吸附法检测骨转换生化标志物(血清骨钙素、血清骨碱性磷酸酶、尿吡啶啉和尿脱氧吡啶啉)。 结果：561例合格受试者进入结果分析。①维生素D受体基因BSMⅠ,TAQⅠ,APAⅠ多态性各基因型间骨密度比较差异无显著性意义(P > 0.05)。②维生素D受体基因BSMⅠ,TAQⅠ,APAⅠ多态性各基因型间骨转换生化标志物比较差异无显著性意义(P > 0.05)。③维生素D受体基因BSMⅠ,TAQⅠ,APAⅠ多态性各基因型间骨质疏松症发生率比较差异无显著性意义(P > 0.05)。④维生素D受体基因BSMⅠ,TAQⅠ,APAⅠ多态性各基因型间绝经后骨折发生率比较差异无显著性意义(P > 0.05)。 结论：维生素D受体基因BSMⅠ,TAQⅠ,APAⅠ多态性与绝经后骨质疏松症无明显关联,不能作为福州地区绝经后妇女骨质疏松的遗传标志。     

骨钙素基因Hind Ⅲ多态性与福州地区汉族绝经后妇女骨密度的相关性*

背景：骨质疏松症是一种多基因遗传病,骨钙素受体基因多态性与骨密度关系存在地域和人群的差异。 目的：观察绝经后妇女骨钙素基因型频率分布及其与骨密度的关系,探讨福州地区汉族绝经后妇女骨质疏松症的遗传易感基因。 方法：用聚合酶链式反应限制性片段长度多态性分析201例汉族绝经后妇女骨钙素基因型,用双能X射线吸收法测定腰椎、股骨颈,大转子和Ward’s三角4个部位骨密度值。 结果与结论：福州地区汉族绝经后妇女骨钙素基因型频率分布符合Hardy-Weinberg定律(χ2=2.29,P > 0.05),基因多态性分布依次为HH 5%、hh 46%、Hh 49%,与福州、北京、广州、台湾地区骨钙素基因Hind Ⅲ位点多态性分布频率差异无显著性意义(P > 0.05)。但是与日本人、白种人差异明显(P < 0.05)。且HH基因型在大转子骨密度明显高于hh型(P < 0.05),但不同基因型在第2~4腰椎、股骨颈、Ward’s三角区的骨密度差异无显著性意义。提示绝经后妇女骨钙素基因型与大转子骨密度可能存在一定关联。     

广西百色地区壮族男性人群骨密度与脂联素基因单核苷酸多态性的关系***

背景：脂联素可在骨代谢中发挥重要作用。 目的：观察脂联素基因单核苷酸多态性与广西百色地区壮族男性骨密度的关系。 方法：选取广西百色地区壮族男性跟骨骨量减少患者,采用单碱基延伸的单核苷酸多态性分型技术对广西百色地区302例壮族男性的脂联素基因的5个单核苷酸多态性位点(rs1063539、rs12495941、rs266729和rs3774261)进行了基因分型。 结果与结论：以5个多态性位点作为自变量的多元 Logistic回归检测结果显示,仅rs3774261多态性与跟骨超声振幅衰减显著相关(OR=1.948,95%CI：1.184~3.203,P < 0.01),并独立于骨量减少的传统危险因素。对基因型进行纯合子与杂合子合并后的协方差分析显示,仅rs3774261的AG+GG与AA基因型的跟骨超声振幅衰减值差异有显著性意义(P < 0.05),AG+GG型对骨密度具有一定的保护作用,AA型是骨密度降低的危险因素。结果证实,脂联素基因第2内含子rs3774261位点多态性与中国百色地区壮族男性骨密度有一定关联。     

雌激素受体β基因多态性与绝经后女性原发性良性阵发性位置性眩晕的相关性分析

目的探讨雌激素受体(ER)β基因多态性与绝经后女性原发性良性阵发性位置性眩晕(BPPV)的关联性。方法选取2015年1月至2017年7月于本科治疗的165例绝经后女性原发性BPPV患者作为病例组,以及同期行健康体检的160例正常绝经的健康女性作为对照组,采用聚合酶链反应-DNA直接测序法检测ERβ基因G1082A、G1730A和CA重复序列多态性,并收集患者临床资料进行分组及统计学分析。结果病例组与对照组比较,两组ERβ基因G1082A、G1730A位点基因型和等位基因分布频率差异均无统计学意义(均P0.05);两组CA重复序列多态性位点基因型分布频率差异具有统计学意义(P0.05),携带短CA重复序列可显著增加绝经后女性原发性BPPV发病风险(OR=1.446,95%CI 1.061～1.969,P=0.019)。结论 ERβ基因CA重复序列多态性可能与绝经后女性原发性BPPV易感性相关,短CA重复序列可能是绝经后女性原发性BPPV的易感基因;ERβ基因G1082A、G1730A多态性与绝经后女性原发性BPPV易感性均无明确关联。     

北京部分汉族男性维生素D受体基因Fok Ⅰ多态性与骨密度的关系

背景：骨质疏松症是受遗传和环境因素共同作用的多因子复杂疾病。维生素D受体基因多态性被认为是调控骨量的重要遗传因素,但在不同种族人群中的研究结果仍存在争议。 目的：观察维生素D受体基因Fok Ⅰ多态性与北京地区部分汉族男性骨密度的关系,以探求北京地区男性骨质疏松症的遗传易感性。 设计、时间及地点：随机对照试验,在2004-09/2007-12在解放军第二炮兵总医院内分泌科和解放军总医院老年病研究所分子生物学实验室共同完成。 对象：筛选2004-09/2006-12长期居住北京地区无血缘关系的20~80岁健康汉族男性230人。 方法：用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析法检测受试者维生素D受体基因Fok Ⅰ基因型,使用双能X射线吸收测定法检测随机抽取的100例受试者腰椎和髋部的骨密度。 主要观察指标：①受试者年龄、身高、体质量。②受试者维生素D受体基因Fok Ⅰ基因型。③受试者L2~4椎体、股骨颈、大转子及Wards三角部位骨密度。 结果：受试者维生素D受体基因Fok Ⅰ的基因型及基因频率的分布为FF 36.96%,Ff 46.96%,ff 16.08%,符合Hardy-Weinberg定律;校正年龄、体质量、身高和体质量指数对骨密度的影响后,40~59岁年龄段男性ff基因型组骨密度较FF,Ff基因型低(P=0.037)。其余各年龄段、各部位ff基因型组骨密度大多低于FF,Ff基因型,但差异无显著性意义(P > 0.05)。 结论：北京地区汉族男性维生素D受体基因Fok Ⅰ多态性分型与骨密度之间可能存在一定关联,该项检测对筛查男性骨质疏松症高危人群的意义需进一步研究。     

金属植入物及Ⅰ型胶原蛋白基因多态性与自体骨移植后脊柱融合效果的相关性★

背景：基础研究表明Ⅰ型胶原蛋白在骨生成、骨的质量及骨折方面作用突出，同时参与骨融合过程，但关于此基因多态性与脊柱融合的关系鲜见报道。 目的：观察Ⅰ型胶原蛋白基因多态性，并探讨其与金属植入物及自体骨移植脊柱融合效果的相关性。 方法：随机选择青岛大学医学院附属医院住院患者中需行脊柱融合的自愿受试者200例，其中行颈椎前路椎体次全切除减压自体髂骨植骨融合钛板内固定者102例，腰椎后路椎板切除减压横突间植骨融合内固定者98例，以223名健康正常人作对照。抽取受试者外周静脉血，并提取白细胞DNA；采用聚合酶链反应扩增目的基因所在的DNA片段，扩增片段长度为293 bp；应用聚合酶链反应-限制性片段长度多态性方法检测外周血白细胞基因组Ⅰ型胶原蛋白基因Pcol2位点多态性，扩增产物经限制性内切酶Eco31I酶切，琼脂糖凝胶电泳观察，有酶切位点用G基因表示，无酶切位点用T基因表示；术前及术后3，6，12个月的X射线片观察植骨融合情况，按照快(< 3个月)、中(3~6个月)、慢(7~12个月)分期进行对比。 结果与结论：两组受试者均存在Ⅰ型胶原蛋白基因Pcol2位点-1997G/T多态性，GG型166例，GT型232例，TT型25例，并发现GG基因型与颈椎前路减压自体髂骨植骨融合有相关性(P=0.004)，该基因型在快组中占50%，明显高于中组(33.3%)和慢组(16.7%)；-1997G/T多态性与腰椎后路横突间植骨融合无相关性(P=0.831)。结果提示Ⅰ型胶原蛋白基因Pcol2位点-1997G/T单核苷酸多态性GG基因型可能是促进颈椎前路自体髂骨植骨融合的重要遗传基因。     

骨密度及下肢血管病变与2型糖尿病的相关性**★

目的：骨质疏松症、糖尿病、动脉粥样硬化均为代谢性疾病，在同一个体常常合并存在。通过分析2型糖尿病患者下肢血管病变不同程度的骨密度变化，可探讨其可能的影响因素。 方法：选取2006-03/10河北医科大学第三医院住院的2 型糖尿病患者140例，男性71例，女性69例，年龄≥45岁（女性绝经1年以上）。患者对检测指标知情同意。按照下肢血管病变严重性进行评分，将入选病例分为正常组、轻度组、中度组和重度组，每组35例。全部受试者均检测正位腰椎及双侧股骨骨密度，并行双下肢动脉彩超。 结果：①年龄、体质量指数、糖尿病病程、绝经年限、血糖水平、胰岛素水平、脂代谢指标控制、尿白蛋白、继发甲状旁腺激素水平、雌激素水平变化越大，腰椎、双侧股骨各部位骨密度差异越明显（P < 0.05）。②腰椎、股骨骨密度与糖尿病病程、年龄、空腹血糖、餐后2 h血糖、糖化血红蛋白、尿白蛋白、胆固醇、低密度脂蛋白胆固醇、女性绝经年限呈负相关，与体质量指数、高密度脂蛋白和雌二醇呈正相关，与三酰甘油和极低密度脂蛋白水平无明显相关。腰椎骨密度与甲状旁腺激素水平正相关，股骨骨密度与空腹胰岛素正相关。③下肢动脉彩色超声动脉硬化程度积分与糖尿病病程、年龄、空腹血糖、餐后2 h血糖、糖化血红蛋白、尿白蛋白、胆固醇、低密度脂蛋白胆固醇、继发甲状旁腺激素水平呈正相关，与雌二醇水平呈负相关，与体质量指数、空腹胰岛素水平、三酰甘油、高密度脂蛋白胆固醇、极低密度脂蛋白胆固醇和绝经年限无明显相关。2型糖尿病下肢血管病变患者较2型糖尿病非下肢血管病变患者骨密度低，且动脉硬化程度越重，骨密度越低，尤以股骨骨密度最为显著。 结论：①糖尿病下肢血管病变与骨密度密切相关。②年龄、血糖、血脂、糖尿病病程、糖尿病肾病、女性雌激素、血继发甲状旁腺激素水平是影响糖尿病患者骨密度及下肢血管病变的共同因素。     

细胞色素P450酶1A2和2C19基因多态性与难治性抑郁症的关联分析

目的探讨细胞色素P450酶(cytochromeP450enzymes,CYP)1A2、2C19基因多态性与难治性抑郁症的关联。方法应用聚合酶链反应(PCR)扩增技术及限制性片段长度多态性(RFLP)测定79例难治性抑郁症患者及107名正常对照者CYP1A2C163A、CYP2C19G681A基因多态性。结果两组间基因型及等位基因分布差异无显著性(χ2=3.605,P>0.05;χ2=3.154,P>0.05)。难治性抑郁症患者对照组间基因型及等位基因分布差异无显著性(χ2=0.853,P>0.05;χ2=0.568,P>0.05)。79名患者中46名接受氟西汀合并小剂量利培酮(0.5～2.0mg/d)治疗,将其分为治疗有效组和无效组,两组间CYP1A2C163A(χ2=0.785,P>0.05;χ2=7.142,P>0.05)CYP2C19G681A(χ2=3.008,P>0.05;χ2=2.722,P>0.05)基因型及等位基因分布差异均无显著性。根据CYP2C19G681A基因多态性将患者分为无突变组(G/G型)和突变组(G/A型和A/A型),两组患者CYP1A2C163A基因型及等位基因分布差异无显著性(χ2=0.252,P>0.05;χ2=0.682,P>0.05)。结论CYP1A2C163A和CYP2C19G681A基因多态性与难治性抑郁症无显著关联,不是影响利培酮对氟西汀增效作用的主要因素。     

Association between estrogen receptor alpha and beta gene polymorphisms and deep vein thrombosis

BACKGROUND: Estrogen and the estrogen receptors alpha (ESR1) and beta (ESR2) play a role in regulating genes, including coagulation and fibrinolysis genes. OBJECTIVE: We investigated the association between ESR1 c.454-397T>C and c.454-351A>G and ESR2 1082A>G and 1730A>G polymorphisms and the risk of deep vein thrombosis (DVT), in 134 patients and 134 controls with acquired risk factors for thrombosis associated with estrogen alterations, such as pregnancy, puerperium, oral contraceptives (OC), and hormone replacement therapy (HRT). We also analysed 134 men with DVT. We investigated the relationship of these polymorphisms and the levels of fibrinogen, protein C (PC), protein S (PS), and antithrombin (AT) activity. METHODS: Gene polymorphisms were identified by using PCR and RFLP. Coagulation methods were used to measure PC, PS, and fibrinogen. Chromogenic methods were used to quantify AT. RESULTS AND CONCLUSIONS: The presence of the AA genotype of the 1730G>A polymorphism (OR=0.18; 95%CI=0.05-0.62) suggests a protective effect for DVT in women using OC. As the GG genotype of the 1730G>A polymorphism is associated with increased PS activity in all control women and women using OC, this suggested that a protective effect must occur by another pathway not related to PS. The AA and AG genotypes of the c.454-351A>G and GG genotype of the 1082G>A polymorphisms are associated with increased fibrinogen concentration in pregnant women. The GG haplotype in the ESR2 gene (P<0.001) was related to factor V Leiden or G20210A mutation in the prothrombin gene, or both, as predictive factors of DVT.     

Cognitive performance in elderly women: significance of the 19bp insertion/deletion polymorphism in the 5' flank of the dopamine beta-hydroxylase gene, educational level, body fat measures, serum triglyceride, alcohol consumption and age

BACKGROUND: Genetic and environmental factors influence cognitive aging. The gene encoding dopamine beta-hydroxylase (DBH) could be one such factor since this hydroxylase converts dopamine to norepinephrine both of which are involved in cognition regulation. OBJECTIVE: To assess the effect of the 19bp insertion/deletion polymorphism in the 5' flank of the DBH gene on cognitive performance in elderly women relative to other factors of cognitive aging. METHODS: We examined a cross-sectional sample of 1371 postmenopausal women. Cognitive abilities were assessed by the 6-item orientation-memory-concentration test. The 19bp insertion/deletion polymorphism of the DBH gene was genotyped and apolipoprotein E (APOE) epsilon4 allele status was determined. In addition blood pressure, body fat mass and blood lipids were measured. Information was also obtained by personal interviews. Data were analyzed by regression analysis. RESULTS: Cognition was univariately associated with DBH genotype (p = 0.04). A univariate association of borderline significance was observed for APOE epsilon4 allele status (p = 0.07). Exclusion of women with severe cognition impairment did not alter the strength of the association with the DBH gene polymorphism markedly (p = 0.06) but obliterated the weak association between APOE epsilon4 allele status and cognition. The association of the DBH gene polymorphism with cognition persisted after adjustment for other variables (p = 0.03). CONCLUSIONS: The 19bp insertion/deletion polymorphism of the DBH gene influences cognition in elderly women and might have a stronger effect than APOE epsilon4 allele status on mild cognitive impairment. Both genetic polymorphisms had a significantly smaller impact on cognition than age, education, alcohol consumption and body fat measures.     

The prothrombin gene G20210A variant and puerperal cerebral venous and sinus thrombosis in South Indian women.

Pregnancy and puerperium raise the risk of thrombotic events, and these risks are likely to be increased in women who are carriers of thrombophilic gene polymorphisms. Prothrombin G20210A variant is reported to be the second most frequent prothrombotic polymorphism in Caucasians. Our aim was to determine the prevalence of this variant in south Indian women and examine its association with cerebral venous and sinus thrombosis occurring during puerperium. We investigated 96 women with puerperal cerebral veno-sinus thrombosis (CVT) and 103 age-matched women with no post-partum complications. We used restriction fragment length polymorphism analysis to identify their genotypes. The prothrombin G20210A variant was not detected in either the CVT patients or the healthy control subjects. Our study on a large series of patients with puerperal CVT shows that the prothrombin G20210A variant is not present in south Indian women and is not associated with puerperal CVT. This study also highlights the fact that there are racial differences in the risk factors for thrombosis, which should be considered when investigating these patients.     

Association between monoamine oxidase A polymorphisms and anger-related personality traits in Korean women

It has been suggested that polymorphisms in the monoamine oxidase A (MAO-A) gene are associated with aggressive and impulsive behaviors. In the present study, we investigated the association of the MAO-A variable number of tandem repeat polymorphism in the promoter region (MAO-A uVNTR) with anger-related personality traits. Specifically, MAO-A uVNTR polymorphisms were examined for associations with the State-Trait Anger Expression Inventory (STAXI) scores in 211 normal Korean women. All subjects were assessed using the STAXI and genotyped for MAO-A uVNTR status. The scores on the STAXI subscales differed significantly among the MAO-A uVNTR polymorphism genotypes in terms of anger expression-out (AX-Out) scores. Post hoc comparisons revealed significant differences between the 3/3 and 4/4, and between 3/4 and 4/4 polymorphisms. However, no significant difference was observed in other STAXI subscale scores among these genotypes. Subjects with the high-activity MAO-A uVNTR had significantly higher AX-Out scores than subjects with other genotypes. MAO-A uVNTR polymorphisms may contribute in part to the expression of anger. These findings support the hypothesis that this polymorphism in the MAO-A gene may be associated with anger-related personality traits in Korean women.     

中国老年人骨量丢失与维生素D受体基因启动子中Cdx-2结合位点的多态性

背景：骨质疏松症是一种与基因有关的骨脆性疾病，维生素D受体基因是主要候选基因之一。 目的：前瞻性调查老年人维生素D受体基因启动子中Cdx-2结合位点多态性与骨密度、骨量丢失的关系。 设计、时间及地点：前瞻性横断面调查，于2000-03/2005-03在沈阳医学院营养与食品卫生学教研室完成。 对象：选取沈阳市某社区无血缘关系、60岁以上的100名汉族健康老年人作为调查对象，性别不限，未服用过维生素D和钙补充剂，均自愿参与调查。 方法：用聚合酶链反应限制性片段长度多态性方法检测维生素D受体基因启动子中Cdx-2结合位点的多态性，应用DPX-L双能X射线吸收仪分别在调查初始和5年后两次测量调查对象的髋部骨密度。 主要观察指标：检测维生素D受体基因启动子中Cdx-2结合位点基因型分布，以协方差分析法分析维生素D受体基因启动子中Cdx-2结合位点多态性与髋部骨密度的关系。 结果：调查人群维生素D受体基因启动子中Cdx-2结合位点基因型频率分布为AA型17%，AG型57%，GG型26%；男女间等位基因型分布差异无显著性意义（P > 0.05）；该人群中等位基因频率分布符合Hardy-Weinberg 定律。无论男女各基因型间年龄、身高和体质量差异均无显著性意义（P > 0.05）。经身高、体质量和年龄校正后，调查初始不同基因型调查对象间股骨颈和大转子的骨密度差异无显著性意义（P > 0.05）；不同基因型调查对象间各部位年骨量丢失率差异也无显著性意义（P > 0.05）。 结论：调查人群维生素D受体基因启动子中Cdx-2结合位点基因型与髋部骨密度及骨量丢失无明显相关性。     

Association between lymphotoxin alpha (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke in North Indian population: a hospital-based case-control study

Purpose: Lymphotoxin alpha (LTA), a proinflammatory cytokine, plays an important role in promoting atherosclerosis which is an independent risk factor for stroke. Recent genetic studies have suggested that polymorphisms in the LTA gene, which affect its expression and biological function, may contribute to the development of stroke. The aim of this case-control study was to determine the association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke. Methods: Genotyping was determined by using SNaPshot method for 250 ischemic stroke (IS) patients, 250 age and sex matched IS free controls, 100 intracerebral hemorrhage (ICH) patients and 100 age and sex matched ICH free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke. The linkage disequilibrium (LD) was analyzed by using HaploView 4.2 software. Results: The distribution of LTA (-252 A/G and -804 C/A) genotypes was consistent with Hardy–Weinberg equilibrium. Adjusted conditional logistic regression analysis showed no significant association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of both IS and ICH. Based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, a significant association between LTA -252 A/G gene polymorphism and small vessel disease subtype of IS under dominant model (OR, 2.06; 95% CI, 1.03–4.12; p value 0.04) with the risk of IS was observed. No LD was observed for both single nucleotide polymorphisms (SNPs) in north Indian population. Conclusion: Neither -252 G/A nor -804 C/A polymorphism of the LTA gene was found to be associated with overall stroke as well as any subtype of IS excluding SVD in North Indian population.     

Assessment of genetic risk for myocardial infarction

Although lifestyle and environmental factors influence the prevalence of myocardial infarction, genetic epidemiological studies have suggested that several genetic variants increase the risk for this condition. We have performed a large-scale association study to identify gene polymorphisms for reliable assessment of the genetic risk of myocardial infarction. The study population comprised 3,483 unrelated Japanese individuals (1,913 men; 1,570 women), including 1,192 subjects with myocardial infarction and 2,291 controls. The genotypes for 164 polymorphisms of 137 candidate genes were determined with an oligonucleotide ligation assay based on analysis of fluorescent microspheres with suspension array technology. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hypercholesterolemia revealed that the 677C-->T (Ala222Val) polymorphism of MTHFR, the 1595C-->G (Ser447Stop) polymorphism of LPL, and the -108/3G-->4G polymorphism of IPF1 were significantly associated with the prevalence of myocardial infarction. A stepwise forward selection procedure demonstrated that IPF1, MTHFR, and LPL genotypes significantly affected the prevalence of myocardial infarction. Combined genotype analysis of these polymorphisms yielded a maximum odds ratio of 2.54 for the combined genotype of TT for MTHFR, CC for LPL, and 3G3G for IPF1. The genotypes for MTHFR, LPL, and IPF1 may prove reliable for assessment of genetic risk for myocardial infarction. Determination of the combined genotype for these genes may contribute to primary, personalized prevention of this condition.