过氧化物酶体增殖物激活受体γC161T基因多态性与糖皮质激素性骨质疏松症的关系

目的 探讨中国人过氧化物酶体增殖物激活受体γ(PPARγ)基因外显子6 C161T多态性与糖皮质激素性骨质疏松症(GIO)的相关关系。方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RELP)方法测定208例正常健康人（Ⅰ组）、168例非GIO患者（Ⅱ组）和104例GIO患者（Ⅲ组）PPARγ基因外显子6 C161T的基因型。应用双能X线骨密度仪(DEXA)测定股骨、腰椎等部位的骨密度。 结果 外显子6 C161T有CC、CT、TT 3种基因型。GIO组CC基因型频率显著低于正常对照组；CT和TT基因型频率显著高于正常对照组。非GIO组、应用激素组（GIO组＋非GIO组）与正常对照组比较，各基因型频率差异均无统计学意义。正常对照组C161T的CC基因型组各部位的骨密度有高于CT和TT基因型组的趋势，但差异无统计学意义。非GIO组和GIO组C161T的CC基因型组腰椎的骨密度明显高于CT和TT基因型组 (P ＜ 0.05)，分别为非GIO组CC型（1.04±0.17） g/cm2，CT+TT型（1.02±0.07） g/cm2；GIO组CC型（0.94±0.12） g/cm2，CT+TT型（0.83±0.08） g/cm2。经年龄、体重指数等因素校正后，差异仍有统计学意义(P ＜ 0.05）。 结论 PPARγ基因C161T基因型在正常人和应用激素患者之间无明显差异，它可能与肾小球肾炎的发病无关。C161T基因型在GIO组和正常对照组之间差异有统计学意义，它可能与糖皮质激素性骨质疏松症的发病有关。PPARγ基因C161T多态性与应用糖皮质激素患者腰椎的骨密度有关。等位基因C可能是骨量的保护因子，它可能与应用糖皮质激素后骨量的丢失有关。     

MTHFR C677T和CBS844 ins 68基因多态性与阿尔茨海默病的相关性研究

目的探讨亚甲基四氢叶酸还原酶(MTHFR)C677T、胱硫醚β合成酶(CBS)844 ins 68 基因多态性与阿尔茨海默病(ADl的相关性。方法运用多聚酶链反应技术检测66例AD病人及 143例正常人MTHFR C677T、CBS 844 ins 68基因多态性。结果 (1)AD病人MTHFR基因中,基因型C/T占56．06％,明显高于对照组的34．97％(P<0．01,RR=0．355);C/C占39．39％,明显低于对照组的 62．94％(P<0．01);T/T占4．25％,与对照组2．09％无明显差异(P>0．05)。AD病人中MTHFR基因等位基因C的频率为67．43％、相对危险率R为0．594,T的频率为32．57％,而对照组的C为80．42％,T为 19．58％,差异有统计学意义(P<0．05)。(2)AD组CBS 844 ins 68 D/D、D/I、I/I基因型频率(％)分别为 78．79、19．69、1．52,对照组分别为78．32、18．88、2．8,其差异无统计学意义(P>0．05)。结论 MTHFR基因突变与AD发生有一定关系,CBS多态性与AD无明显相关。     

Interaction between the dopamine D4 receptor and the serotonin transporter promoter polymorphisms in alcohol and tobacco use among 15-year-olds

Early onset of alcohol and tobacco use during adolescence increases the risk for establishing a substance use disorder in adulthood. Both alcohol and nicotine stimulate the dopamine (DA) and the serotonin (5-HT) systems. The DA system has been implicated in the mediation of the rewarding effects of self-administered drugs of abuse. A possible role of an interaction between these neurotransmitter systems in substance use behavior has been suggested but is as yet unknown. The present study was designed to examine the influence of the DA D4 receptor (DRD4) and the serotonin transporter (5-HTT) genotype and their interaction on adolescent alcohol and tobacco experimentation. Participants were from a longitudinal study of a birth cohort consisting initially of 384 children from a high-risk community sample. At the age of 15 years, adolescents completed a self-report questionnaire measuring tobacco and alcohol consumption. DNA was taken from 305 participants (146 boys, 159 girls) and genotyped for the DRD4 exon III and the 5-HTTLPR polymorphisms. The DRD4 7-repeat allele was associated with greater smoking and drinking involvement in boys. In girls, a significant DRD4 × 5-HTT interaction was detected. Girls without the DRD4 7-repeat allele and who were homozygous for the long allele of 5-HTTLPR displayed the highest smoking and drinking activity. The genetic and potential molecular background underlying adolescent vulnerability to substance abuse is discussed.     

血管性危险因子与Alzheimer病痴呆进展的相关性研究

目的研究血管性危险因子载脂蛋白E(ApoE)基因、低密度脂蛋白受体相关蛋白(LRP)基因以及血管紧张素转换酶(ACE)基因与Alzheimer病(AD)痴呆进展恶化之间的相关性。方法应用简易精神状态检查表(MMSE)和痴呆严重程度临床评定量表(CDR),对78例晚发性AD患者进行为期2年的随访研究,并应用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)技术或直接通过PCR方法,分析这些患者ApoE、LRP与ACE基因型。结果(1)ApoE基因ε4等位基因和ApoEε4携带者与AD痴呆进展恶化之间在统计学上均有显著性关联(P<0.05);(2)非恶化组ApoE基因ε3等位基因频率比恶化组增多(P<0.05);(3)ACE基因I等位基因频率在两组之间差异显著(P<0.05);(4)LRP基因的等位基因频率在两组之间无显著性差异(P>0.05)。结论ApoEε4等位基因可能是AD进展恶化的遗传危险因子,ApoEε3等位基因则可能有保护效应;ACE I等位基因亦可能是AD进展恶化的遗传危险因子。     

脂蛋白脂酶Hind Ⅲ基因多态性与动脉硬化性脑梗死的关系

目的研究脂蛋白脂酶HindⅢ基因多态性与动脉硬化性脑梗死发病的关系及其对血脂、颈动脉斑块的影响。方法选择166例动脉硬化性脑梗死患者，采用聚合酶链反应-限制性片段长度多态性分析检测脂蛋白脂酶的HindⅢ基因多态性，颈动脉超声多普勒检查颈总动脉内膜中层厚度和颈动脉斑块，并与72名健康对照比较。结果在脑梗死组中H＋H＋基因型频率和H＋等位基因频率明显高于对照组（OR=2．267，P=0．004；OR=1．903，P=0．004），而血脂水平、颈总动脉内膜中层厚度、颈动脉斑块分级与对照组比较差异无统计学意义。结论脂蛋白脂酶的HindⅢ基因多态性与脑梗死的关系密切，H＋H＋基因型可能是脑梗死的危险因素。     

Cav1.1基因26内含子67位点A/G多态性与甲状腺功能亢进性周期性瘫痪的相关性研究

目的探讨钙通道α1亚基（Cav1．1）基因26内含子-67A／G多态性与男性甲状腺功能亢进（简称甲亢）性周期性瘫痪（TPP）的相关性。方法采用多聚酶链反应-单链构象多态性（PCR-SSCP）方法检测46例男性TPP患者（TPP组）、68例男性甲亢患者（GD组）和72名男性健康对照者（CON组）Cav1．1基因26内含子-67A／G多态性。分析比较此多态位点基因型和等位基因在不同人群中分布的差异。结果（1）TPP组、GD组及CON组AG＋GG基因型频率分别为47．83％、14．71％、29．17％，G等位基因频率分别为44．57％、13．24％、27．78％。（2）TPP组AG＋GG基因型频率明显高于GD组和CON组（OR=5．32，P〈0．01；OR=2．23，P=0．04），TPP组G等位基因频率明显高于GD组和CON组（OR=5．27，P〈0．01；OR=2．09，P=0．008）。结论Cav1．1基因26内含子-67位点A／G多态性与男性TPP有相关性。     

CYP2A6基因多态性对丙戊酸钠血药浓度的影响

目的探讨细胞色素P4502A6(CYP2A6)基因多态性对丙戊酸钠血药浓度的影响。方法选择单药服用丙戊酸钠的癫患者98例,应用巢式PCR(nested-primerpolymerasechainreaction)方法分析其CYP2A6基因型,分析等位基因CYP2A6*1及CYP2A6*4;同时应用荧光偏振免疫法(FPIA)测定患者丙戊酸钠的血药浓度。结果98例患者中CYP2A6基因型为*1/*1者73例(74·5%),*1/*4者24例(24·5%),*4/*4者1例(1·0%),根据基因型分为A组(CYP2A6*1/*1)和B组(CYP2A6*1/*4或CYP2A6*4/*4)。B组患者丙戊酸钠的标准血药浓度平均值(4·1393±0·2793)较A组(3·3486±0·3919)高,差异有统计学意义(P<0·05)。结论CYP2A6基因多态性影响丙戊酸钠的血药浓度,含有CYP2A6*4等位基因的患者应用丙戊酸钠应较常规降低用量。     

Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C

Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both stroke subtypes in patients with methylenetetrahydrofolate reductase gene polymorphisms. Therefore, we examined whether the C677T and A1298C polymorphisms of MTHFR gene are genetic risk factors for both ischemic and hemorrhagic stroke in a Turkish Caucasian population. In a case-control study, 120 total unrelated stroke patients (92 ischemic stroke, 28 hemorrhagic stroke), and 259 healthy controls were genotyped for C677T and A1298C polymorphisms of the MTHFR gene using a PCR-RFLP based-method. The MTHFR 1298C allele (chi(2)=8.589; P=0.014), C1298C genotype (OR=2.544; P=0.004), and C677C/C1298C compound genotype (OR=3.020; P=0.001) were associated with overall stroke. The MTHFR 1298C allele (chi(2)=11.166; P=0.004), C1298C genotype (OR=2.950; P=0.001), and C677C/C1298C compound genotype (OR=3.463, P=0.0001) were strongly associated with ischemic stroke. Interestingly however, the MTHFR 677T allele (chi(2)=6.033; P=0.049), T677T genotype (OR=3.120; P=0.014), and T677T/A1298A compound genotype (OR=4.211; P=0.002) were associated with hemorrhagic stroke. In conclusion, the C677T and A1298C polymorphisms of the MTHFR gene are genetic risk factors for hamorrhagic and ischemic stroke respectively, independent of other atherothrombotic risk factors.     

谷胱甘肽硫转移酶基因多态性与精子形成的研究进展

精子发生受到诸多有序基因的表达与调控,这些特异基因的遗传多态性可能影响精子的发生。谷胱甘肽硫转移酶是一组多功能同工酶,属于II相反应代谢的超家族酶系,其通过催化还原型谷胱甘肽与亲电物质发生轭合反应,降低该亲电物质的活性、加速其排泄,达到解毒的效果。研究发现,谷胱甘肽硫转移酶基因多态性与精子发生可能存在密切关系。