广西地区汉族2型糖尿病患者脂联素基因多态性研究

目的：研究脂联素基因外显子2单核苷酸多态性（SNP）＋45T→G多态性与广西地区汉族2型糖尿病（T2DM）、肥胖及胰岛素抵抗（ IR）的关系。方法：运用聚合酶链反应-限制性片段长度多态性（ PCR-RFLP）的方法,对313例无亲缘关系的广西地区汉族人群的正常糖耐量（NGT95例）、糖耐量减低（IGT103例）和T2DM115例检测脂联素基因外显子2的多态性,并与代谢值进行相关性研究。结果：广西地区汉族人群中含脂联素基因外显子2的SNP＋45GG基因型的人群高密度脂蛋白（ HDL-C）水平低于TT、TG基因型的人群（P〈0.05）,HOMA-IR高组的GG基因型相对于TT基因型的OR为2.876（95%CI：1.141~7.248）,即GG基因型发生IR的相对危险度是TT基因型的2.876倍。结论：汉族人群中,脂联素基因SNPs＋45 TT基因型的HDL-C较GG基因型频率高;GG基因型较TT基因型人群易产生IR。但汉族人群SNPs＋45基因型与T2DM及肥胖无关。     

Effect of genetic polymorphism of UCP2-866 G/A on repaglinide response in Chinese patients with type 2 diabetes

The aim of the present study was to evaluate the impact of the UCP2-866 G/A polymorphism on the efficacy of repaglinide in treating patients with diabetes mellitus type 2 (T2DM). 370 patients with T2DM and 166 healthy volunteers were enrolled to identify UCP2-866 G/A genotypes. 16 patients with GG genotype, 14 with GA genotype and 11 with AA genotype of UCP2-866 G/A underwent an 8-week repaglinide treatment regimen. There were no differences in allele frequency of UCP2-866 G/A between T2DM patients and control subjects. The patient with AA genotype of UCP2-866 G/A had higher levels of fasting plasma glucose (FPG), 30-min and 2-h postload plasma glucose, glycated haemoglobin (HbA1c), and lower concentrations of 30-min and 2-h postload plasma insulin, homeostasis model assessment of beta cell function (HOMA-beta), deltaI30/deltaG30 compared with GG genotype. After repaglinide treatment for 8 consecutive weeks, we found that A allele carriers of UCP2 in the T2DM patients had smaller decrease in FPG (P < 0.05) and HbA1c (P < 0.05), and smaller increase in 30-min postload plasma insulin (P < 0.01) compared with GG genotypes. We demonstrated that UCP2-866 G/A polymorphism is associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.     

脂联素受体1基因-102T/G多态位点与山西省汉族人2型糖尿病的关系

目的研究脂联素受体1(AdipoR1)基因-102T/G多态位点与山西汉族人2型糖尿病的关系。方法应用序列特异性引物-聚合酶链反应技术(PCR-SSP)检测50例2型糖尿病患者和50名健康对照者AdipoR1-102T/G单核苷酸多态性位点基因型,并测定所选人群的临床指标。结果①基因型及等位基因频率分布在2型糖尿病患者和健康对照组人群中差异无统计学意义(P>0.05)。②健康对照组人群中,G等位基因携带者空腹血糖较TT基因型者低(P<0.01)。③2型糖尿病患者中,G等位基因携带者空腹胰岛素(P<0.01)、胰岛素抵抗指数(P<0.05)及空腹血糖(P<0.05)较TT基因型者低。结论AdipoR1基因与山西汉族人群糖代谢及胰岛素抵抗相关,与2型糖尿病无关。     

脂联素基N+45T/G多态性与原发性高血压相关性的研究

目的:了解脂联素基因 45T/G多态性在原发性高血压(EH)患者中的分布,探讨该多态性与血浆脂联素浓度的相关性。方法:采用聚合酶链式反应-限制性内切酶长度多态性(PCR-RFLP)技术,对151例原发性高血压患者和100例正常对照者脂联素基因 45T/G多态性进行基因分型。采用ELISA法测定血浆脂联素浓度。结果:(1)原发性高血压组G/G基因型频率明显高于正常对照组(P<0.01),G等位基因频率也明显高于正常对照组(P<0.01),T等位基因频率明显低于正常对照组(P<0.01)。(2)G/G T/G基因型的血浆脂联素浓度与T/T基因型差异有统计学意义(P<0.01)(。3)原发性高血压组血浆脂联素浓度低于正常对照组,差异有统计学意义(P<0.01)。结论:脂联素基因 45T/G多态性、血浆脂联素浓度与高血压有相关性,提示脂联素基因可能是原发性高血压的一个新易感基因。     

脂联素基因启动子-11377（C/G）基因多态性与中国2型糖尿病和罗格列酮降糖疗效的相关性研究

目的：探讨脂联素基因SNP-11377（C/G）与中国汉族2型糖尿病（T2D）的关系及对罗格列酮降糖疗效的影响。方法：应用PCR-RFLP方法对255名T2D和120名健康对照者进行-11377（C/G）基因分型,选取42个不同基因型的T2D患者每天早饭时口服罗格列酮4mg,连续服药12周。测定用药前后的TG、空腹血糖（FPG）、餐后血糖（PPG）、糖化血红蛋白（HbAlc）、空腹胰岛素（FINS）、餐后胰岛素（PINS）、TC、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、胰岛素抵抗指数（HOMA-IR）和脂联素水平。结果：T2D组SNP-11377等位基因频率与基因型频率明显高于健康对照组（P〈0.05）,并且随着G等位基因的增加,患者的脂联素水平（P〈0.01）明显降低,FINS（P〈0.05）和HOMA-IR水平（P〈0.05）明显增高。在服用罗格列酮后,CC型FPG、PPG和HOMA-IR的降低幅度明显高于突变型（CG＋GG）（P〈0.05）,而CC型脂联素升高幅度明显高于突变型（P〈0.01）。结论：脂联素基因启动子-11377C/G遗传变异与胰岛素抵抗和T2D有关,并且可能影响罗格列酮的降糖疗效。     

钙蛋白酶10基因多态性与2型糖尿病胰岛素抵抗的研究

目的:观察天津地区汉族人群中是否存在钙蛋白酶10(CAPN10)UC SNP43G/A等位基因多态性,并探讨与2型糖尿病(T2DM)及胰岛素抵抗(IR)的关系。方法:随机抽取正常人125例(对照组)和2型糖尿患者255例(T2DM组)外周血白细胞基因组DNA,采用PCR-RFLP方法对CAPN10 UC SNP 43G/A基因多态性进行筛查,对突变基因进行克隆测序分析。根据T2DM组中是否有CAPN10 UC SNP43基因突变,分为CAPN10 UC SNP43(G/G型)和CAPN10 UC SNP43(G/A A/A型)2组。结果:T2DM组和对照组G等位基因的频率比较差异无统计学意义(P>0.05)。G/G型组和G/A A/A型组的BMI、空腹胰岛素(FINS)、HOMA-IR指数、空腹C-肽(C-P)、三酰甘油(TG)2组之间差异有统计学意义(P<0.05或P<0.01),G/G型组高于G/A A/A型组。结论:在中国天津地区汉族人群中存在CAPN10 UC SNP 43 G/A基因多态性,但与天津地区汉族人群T2DM无相关性,与IR相关的一些代谢指标相关,可能部分造成了2型糖尿病胰岛素抵抗。     

The association of adiponectin allele 45T/G and -11377C/G polymorphisms with Type 2 diabetes and rosiglitazone response in Chinese patients

AIMS

The aim of the present study was to evaluate the impact of adiponectin allele T45G and C-11377G genetic polymorphisms on efficacy of rosiglitazone in Chinese patients with type 2 diabetes (T2D).

METHODS

Patients with T2D (n = 255) and 120 healthy volunteers were enrolled to identify 45T/G and –11377C/G genotypes by polymerase chain reaction-restriction fragment length polymorphism assay. Forty-two T2D patients with different 45T/G or –11377C/G genotypes received orally rosiglitazone as a single-dose therapy (4 mg day-1 p.o.) for 12 weeks. Serum triglyceride, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin, fasting serum insulin, postprandial serum insulin, total cholesterol, homeostasis model assessment for insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol (HDL-c) and adiponectin concentration were determined before and after rosiglitazone treatment.

RESULTS

We showed an attenuated rosiglitazone effect in patients with –11377CG+GG heterozygote genotype on FPG, PPG, HOMA-IR compared with –11377CC homozygote genotype. However, we found an enhanced rosiglitazone effect on serum adiponectin concentration in patients with –11377CC homozygote genotype compared with –11377CG+GG heterozygote genotype (P = 0.000) and in patients with 45TG + GG heterozygote genotype compared with 45TT homozygote genotype (P = 0.018). Finally, our results showed that there was an enhanced effect in patients with –11377/45 CGTT diplotype compared with other discovered diplotypes on FPG (P = 0.001) and PPG (P = 0.003) after rosiglitazone treatment.

CONCLUSIONS

These data suggest that the adiponectin allele 45T/G and –11377C/G polymorphisms are significantly associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese patients with T2D.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Rosiglitazone is able to increase serum adiponectin levels significantly in Type 2 diabetic patients.
• The role of genetic factors that determine the marked interindividual variability in glucose-lowering efficacy of rosiglitazone in Chinese patients is not known.
• The current study was designed to evaluate the impact of the adiponectin common allele 45T/G and −11377C/G polymorphisms on the response to rosiglitazone monotherapy in Chinese patients with Type 2 diabetes (T2D).

WHAT THIS STUDY ADDS

• The genetic polymorphisms of adiponectin alleles 45T/G and −11377C/G as well as their common diplotypes are significantly associated with an attenuated fasting plasma glucose, postprandial plasma glucose and homeostasis model assessment for insulin resistance as well as an enhanced adiponectin concentration in Chinese patients with T2D after rosiglitazone treatment.

     

2型糖尿病患者脂联素与视网膜病变的相关性研究

目的研究2型糖尿病（T2DM）患者血浆脂联素（APN）水平及脂联素基因启动子区-11377位点单核苷酸多态性（SNP）与糖尿病视网膜病变（DR）之间的关系。方法运用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术,对200例T2DM患者[无DR（NDR）组82例、非增殖型DR（NP-DR）组72例、增殖型DR（PDR）组46例],检测APN基因启动子SNP-11377C→G多态性,同时检测血浆APN浓度、血脂、血糖、空腹胰岛素,比较各组基因型和等位基因频率,并分析各指标间的相关性。结果①APN水平随视网膜病变程度呈递增趋势NDR、NPDR、PDR各分别为（6.11±2.77）,（7.49±3.84）,（9.83±4.97）mg/L,其中PDR组显著高于NDR和NPDR组（P〈0.01）,NPDR组显著高于NDR组（P〈0.05）;②APN水平与HOMA-IR呈负相关（r=-0.203,P〈0.01）;③APN基因启动子SNP-11377C→G的基因型和等位基因频率分布在NDR组、DR组间差异无统计学意义（P〉0.05）。基因型（CC型、CG型和GG型）的血清APN水平差异无统计学意义（P〉0.05）。结论T2DM患者血APN水平随糖尿病视网膜病变进展而增高。未发现福建地区T2DM患者APN基因启动子区-11377C→G多态性与DR明显相关。     

脂联素45 T/G基因多态性对利拉鲁肽治疗2型糖尿病患者的临床疗效

目的:研究脂联素45(APM1-45)T/G基因遗传变异对利拉鲁肽治疗2型糖尿病(T2DM)患者的临床疗效以及对T2DM易感性的影响。方法:选取2017年7月至2019年11月期间海口市第三人民医院收治的T2DM患者共95例作为研究对象,均给予利拉鲁肽进行为期14周的治疗,记录不同基因型患者治疗前后的血糖水平、BMI指数和mRNA相对表达等指标变化,统计不良反应的发生情况。结果:APM1-45(rs2241766)位点在研究人群中的基因分布频率为:TT型46例(48.42%),TG型43例(45.26%),GG型6例(6.32%),三种基因型分布频率符合哈迪温伯格平衡(P=0.328)。治疗后,各组患者的餐后2小时血糖(2h PG)、糖化血红蛋白(HbA1c)、空腹血糖(FPG)和BMI相关指标相比治疗前均下降明显,且存在统计学差异(P<0.05);TT基因型患者的各项指标与TG/GG基因型患者相比,下降更多,但二者相比不存在统计学差异(P>0.05)。mRNA相对表达方面,相对于TG/GG基因型患者,TT基因型患者的mRNA的相对表达明显偏低,二者差异具有统计学意义(P<0.05)。患者整体不良反应发生情况较少,各组之间无统计学差异。结论:对2型糖尿病患者,利拉鲁肽进行治疗具有明显效果,在显著降低血糖水平、控制体质量的同时,不良反应发生率较低,G等位基因与T2DM易感性存在一定的相关性,而T等位基因携带者对利拉鲁肽的治疗表现出更优的效果。     

Serine racemase rs391300 G/A polymorphism influences the therapeutic efficacy of metformin in Chinese patients with diabetes mellitus type 2

1. The aim of this study was to investigate the association of the serine racemase (SRR) rs391300 G/A polymorphism with the risk of diabetes mellitus type 2 (T2DM) and to assess the impacts of the polymorphism on the therapeutic efficacy of metformin in Chinese patients. 2. A case-control study of 402 patients with T2DM and 171 healthy controls was conducted. The SRR rs391300 polymorphism was genotyped in all participants using the ABI 3700 automated sequencer. Forty-four recent-onset T2DM patients with different rs391300 genotypes were selected to receive 500 mg metformin orally daily for 12 consecutive weeks as monotherapy. Serum fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated haemoglobin (HbA1c), fasting serum insulin (FINS), postprandial serum insulin (PINS), triglycerol (TG), cholesterol (CHO), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), homeostasis model assessment for insulin resistance (HOMA-IR), and body mass index (BMI) were determined before and after metformin treatment. 3. The distribution frequencies of rs391300 were in agreement with Hardy-Weinberg equilibrium (P > 0.05). After treatment with metformin, the values of BMI, FPG, PPG, PINS, HbA1c, CHO, and TG decreased significantly (P < 0.01), whereas FINS increased (P < 0.001), in patients with T2DM. Patients with the GA or AA genotype of rs391300 showed better improvements in the levels of FPG, PPG, and CHO (P < 0.05) than individuals with the GG genotype. 4. The SRR rs391300 polymorphism was associated with the therapeutic efficacy of metformin in Chinese patients with T2DM.     

SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in Chinese type 2 diabetics treated with metformin

Aim:

To investigate the potential relationship between the SLC22A2 gene polymorphism and blood lactate concentration in Shanghai Hans suffering from type 2 diabetes mellitus (T2DM).

Methods:

The SLC22A2 single nucleotide polymorphism (SNP) 808G/T was genotyped in 400 T2DM patients, including a metformin-treated group (n=200) and a non-metformin-treated group (n=200). Fasting plasma lactic acid levels were measured with an enzyme-electrode assay. Biochemical indexes, including plasma alanine aminotransferase (ALT), creatinine (Cr), and glycolated hemoglobin (HbA1c), were also measured.

Results:

The fasting plasma lactate concentration in the metformin-treated group was significantly higher than that in the non-metformin-treated group (1.29±0.45 mmol/L vs 1.18±0.44 mmol/L, P=0.015). Additionally, the ratio of patients with hyperlactacidemia was 8% (16/200) for the metformin-treated group and 5.5% (11/200) for the non-metformin-treated group, with no lactic acidosis found in either group. The frequency of the SLC22A2 808G/T T allele was 12.9%. Patients with the mutant genotype (TT) had a higher blood lactate concentration in the metformin-treated group than those in the non-metformin-treated group (t=2.492, P=0.013). This trend was not observed in the GG and GT genotypes when compared with metformin-treated and non-metformin-treated groups. Patients with the mutant genotype (TT) in the metformin-treated group also had a higher incidence of hyperlactacidemia compared with the GG genotype (40.0% vs 6.9%, P=0.050) in the metformin-treated group and the GG (6.0%, P=0.042) or GT (4.3%, P=0.043) genotypes in the non-metformin-treated group. In the metformin-treated group, there were significant gender differences in lactate concentrations in the TT (2.18±0.15 vs 1.04±0.27 mmol/L, P=0.008) and GG genotypes (1.40±0.51 vs 1.19±0.35 mmol/L, P=0.004). The lactate levels of women with the TT genotype were the highest in the metformin-treated group, but differences in lactate levels among the genotypes were not observed in the non-metformin-treated group.

Conclusion:

There is an 808G/T polymorphism in the SLC22A2 gene in Chinese Hans with T2DM. The 808G>T variance in the SLC22A2 gene can affect the plasma lactate level and the incidence of hyperlactacidemia in T2DM patients undergoing metformin therapy. Additionally, the female patients carrying the TT genotype are prone to lactatemia.     

高血糖人群血清脂联素、胰岛素抵抗指数和血管内皮功能变化及相关性研究

目的探讨高血糖人群血清脂联素、胰岛素抵抗（IR）指数和血管内皮功能变化及相关性。方法从35。55岁健康体检人群经口服葡萄糖耐量试验（OGTT）筛选出糖耐量正常（NGT）43例,空腹血糖调节受损（IFG）47例,糖耐量受损（IGT）52例,糖尿病（DM）41例,检测并比较血糖、血清脂联素水平、IR指数及血管内皮功能。结果空腹胰岛素水平在IFG、IGT、DM3组均高于NGT组（P〈0．05）;餐后2h胰岛素水平从DM、IGT、IFG组到NGT组依次降低,且差异有统计学意义（P〈0．05）。IFG、IGT、DM组IR指数明显高于NGT组,DM组IR指数高于IFG和IGT组（P〈0．05）。血清脂联素水平及血管内皮功能在NGT、IFG、IGT、DM组依次降低（P〈0．05）。脂联素与空腹血糖、IR指数呈负相关（P〈0．01）。结论血清脂联素水平、IR指数和血管内皮功能可作为OGTT异常人群动脉硬化的早期监测指标。     

CYP1B1 SNP rs1056827,rs1056836基因多态性与乳腺癌关联研究

目的：研究CYP1B1 SNP rs1056827,rs1056836基因多态性与乳腺癌的关联.方法：应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测CYP1B1 SNP rs1056827,rs1056836基因多态性,比较乳腺癌患者组与健康志愿者对照组CYP1B1 SNP rs1056827,rs1056836基因型的分布频率差异及等位基因频率差异.结果：120例乳腺癌患者组和127例健康志愿者对照组CYP1B1 SNP rs1056827基因型分布频率野生型GG为48.33/65.35％,杂合型GT为40.83/29.13％,突变型TT为10.83/5.51％,两组比较x2为7.71,0.01＜ P＜0.05,等位基因频率野生型G为68.75/79.92％,突变型T为31.25/20.08％,两组比较x2为8.11,P＜0.01;CYP1B1SNP rs1056836基因型分布频率野生型CC为49.17/66.93％,杂合型CG为37.50/26.77％,突变型GG为13.33/6.29％,两组比较x2为8.70,0.01＜P＜0.05,等位基因频率野生型C为67.92/80.31％,突变型G为32.08/19.68％,二组比较x2为8.73,P＜0.01.结论：乳腺癌患者组与健康志愿者对照组CYP1B1 SNP rs1056827,rs1056836基因型分布频率和等位基因频率差异有显著性,提示乳腺癌的发生可能与CYP1B1 SNP rs1056827,rs1056836基因多态性具有某种关联.     

组织激肽释放酶基因多态性A1789G 对高血压患者血浆肌酐水平的影响

目的:探讨组织激肽释放酶基因多态性对高血压患者血浆肌酐水平的影响.方法:用聚合酶链反应-限制性片段长度多态性( PCR-RFLP)方法对 733 例高血压患者的组织激肽释放酶基因 A1789G 多态位点进行基因分型,用线性回归模型分析基因型与血浆肌酐水平之间的关系,用方差分析分析基因型和血压对血浆肌酐水平的交互影响.结果:携带突变型等位基因1789G(基因型AG或GG)高血压患者较携带野生型等位基因A1789(基因型AA)患者的血浆肌酐水平明显升高,且血浆肌酐水平随着血压的升高而升高.结论:组织激肽释放酶基因多态性对高血压患者的血浆肌酐水平产生明显影响,A1789G 多态位点是高血压患者血浆肌酐清除率下降的一个危险因素.     

CBR3 rs1048303位点基因多态性与2型糖尿病相关性及其对瑞格列奈疗效的影响

目的：分析CBR3rs10483032基因多态性在中国淮海地区汉族2型糖尿病（T2DM）患者与正常人群中的分布特征,并探讨该遗传多态性与T2DM易感性的关联及其对瑞格列奈疗效的影响。方法：采用三维聚丙烯酰胺凝胶DNA芯片对180名T2DM患者和101名健康对照者进行CBR3rs10483032基因型分析;81名初诊初治的T2DM患者口服瑞格列奈1 mg,tid,持续8周;服药前和服药第8周末收集静脉血标本,测定糖脂代谢相关指标。应用非参数检验、两样本t检验、配对t检验和χ²检验进行统计学分析。结果：CBR3 rs10483032位点G等位基因频率在T2DM组和健康对照组间分别为17.50%和8.91%,差异具有显著性（P<0.01）。在中国淮海地区汉族T2DM患者中,CBR3 rs10483032位点AG/GG基因型患者的空腹血清胰岛素（FINS）、餐后血清胰岛素（PINS）、稳态模型胰岛素抵抗指数（HOMA-IR）显著高于AA基因型患者,差异有显著性（P<0.05）。瑞格列奈连续治疗8周后,2组基因型之间各临床指标无明显差异（P>0.05）。结论：CBR3 rs10483032位点基因型和等位基因频率在T2DM患者及健康人群中分布存在明显差异,与中国淮海地区汉族人群T2DM发生相关;CBR3 rs10483032位点G等位基因携带者可能通过影响FINS、PINS、HOMA-IR值增加患T2DM风险。瑞格列奈治疗后,CBR3 rs10483032位点多态性与瑞格列奈疗效无关。     

IL-10 基因多态性及血清水平与颅内动脉瘤发病的关系

目的 分析白细胞介素（IL）-10 基因启动子区－ 1082G/A、－ 819C/T 单核苷酸多态性（SNP）及血清 IL-10 水平与颅内动脉瘤（IAs）发病的关系。 方法 运用 PCR 及 DNA 直接测序的方法, 检测 206 例 IAs 患者（IAs 组）和 187 例非 IAs 患者（对照组）的 IL-10 基因启动子区 SNP 位点, － 1082G/A、－ 819C/T 的基因型频率和等位基因频率, χ2检验分析 IAs 组和对照组之间的差异; 采用 ELISA 法检测血清中 IL-10 水平, t 检验分析 2 组之间的差异。 结果 IL-10 基因启动子区－ 1082G/A 位点的 GG 基因型和 GA＋ AA 基因型, 以及 G 等位基因和 A 等位基因频率比较, IAs 组较对照组 GA＋ AA 基因型以及 A 等位基因频率更高, 差异均有统计学意义（P < 0.01）, GA＋ AA 基因型（OR 值为 4.137, 95%CI 2.476~6.914）和 A 等位基因（OR 值为 3.368, 95%CI 2.476~4.583）携带者有更高的 IAs 发病风险; IL-10 基因启动子区－ 819C/T 位点的 CC 基因型和 CT＋ TT 基因型以及 C 等位基因和 T 等位基因频率比较, IAs 组较对照组 CT＋ TT 基因型以及 T 等位基因频率更高, 差异均有统计学意义（P < 0.01）, CT＋ TT 基因型（OR 值为 3.393, 95% CI 1.952~5.900）和 T 等位基因（OR 值为 3.764, 95%CI 2.730~5.192）携带者有更高的 IAs 发病风险。 IAs 组血清 IL- 10 水平低于对照组（P < 0.01）。 结论 IL-10 基因启动子区 SNP 影响 IL-10 表达,IL-10 基因启动子区－ 1082G/A、－ 819C/T 多态性与 IAs 的发病有关。     

高血压合并2型糖尿病患者血浆脂联素与血管内皮功能相关性研究

目的：探讨高血压（EH）合并2型糖尿病（T2DM）患者血浆Adiponectin水平与血管内皮功能的关系。方法：选取研究对象105例根据标准分为正常对照组（NC组）、原发性高血压组（EH组）、高血压合并2型糖尿病组（EH＋T2DM组）,各组分别测定脂联素（Adiponectin）、血栓调节蛋白（Tm）、一氧化氮（NO）,并进行对比及相关分析。结果：与NC组比较,EH＋T2DM组和EH组Tm明显增高（P〈0.05）,血浆Adiponectin和NO明显降低（P〈0.05）。与EH组比较,EH＋T2DM组的Tm明显增高,血浆Adiponectin和NO明显降低（P〈0.05）。EH＋T2DM组血浆Adiponectin水平与Tm呈显著负相关（r=-0.353、P〈0.05）;与NO呈显著正相关（r=0.279,P〈0.05）;Tm与NO呈明显负相关（r=-0.319,P〈0.05）。血浆Adiponectin和NO是平均动脉压独立的影响因素。结论：EH患者体内存在Adiponectin、NO和Tm的异常表达,合并T2DM患者更为显著。血浆Adiponectin可能通过调节血管内皮功能进而在EH、EH合并T2DM的发病机制中具有重要作用,此为早期干预EH＋T2DM提供了理论依据。     

KCNQ1 gene polymorphisms are associated with the therapeutic efficacy of repaglinide in Chinese Type 2 diabetic patients

The present study evaluated the effects of KCNQ1 rs2237892 and rs2237895 polymorphisms on repaglinide efficacy in Chinese patients with Type 2 diabetes mellitus (T2DM). In all, 367 T2DM patients and 214 controls were genotyped. Forty of the T2DM patients were randomly selected to undergo 8 weeks repaglinide treatment. The frequency of the rs2237892 allele was lower in the T2DM patients than in the control group (P < 0.05). The frequency of the rs2237895 C allele was higher in T2DM patients than in healthy control subjects (P < 0.05). Diabetic patients with the rs2237892 risk C allele had lower fasting insulin levels (P < 0.01) and homeostasis model assessment of insulin resistance (HOMA-IR; P < 0.01) values than carriers of the T allele. Diabetic patients with the rs2237895 risk C allele had higher fasting plasma glucose (P < 0.01), postprandial plasma glucose (PPG) levels (P < 0.01) and HOMA-IR values (P < 0.01) than those with the A allele. Following repaglinide treatment, those T2DM patients with the rs2237892 T allele and rs2237895 C allele were more likely to have a positive response to repaglinide in terms of PPG levels (P < 0.05) than T2DM patients with the rs2237892 CC and rs2237895 AA genotypes. In conclusion, KCNQ1 rs2237892 and rs2237895 polymorphisms were found to be associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.     

miR-137 基因 rs1625579 位点多态性与精神分裂症患者 认知功能的关联性研究

摘要： 目的 探讨微小 RNA-137 （miR-137） 单核苷酸多态性 （SNP） 位点 rs1625579 多态性与精神分裂症患者认 知功能的相关性。方法 选取 250 例精神分裂症患者, 采用阳性和阴性症状量表（PANSS）评估精神分裂症患者症 状, 简明精神分裂症认知评估测验量表 （BACS） 评估精神分裂症患者的认知功能。并收集患者外周血液, 采用 SNaP⁃ shot 技术对 rs1625579 位点进行基因分型。比较该位点不同基因型的症状及认知功能差异。结果 TT、 GT、 GG 基 因型分别为 221 例 （88.4%）、 28 例 （11.2%）、 1 例 （0.4%）。TT 基因型和 G 等位基因 （GG+GT） 携带者 PANSS 评分差异 无统计学意义。BACS 测验结果显示, 除数字序列测验 TT 基因型患者得分低于 G 等位基因 （GG+GT） 携带者外 （P < 0.05）, 语义流畅性测验、 字词流畅性测验、 言语记忆测验、 代币运动、 伦敦塔测验、 符号编码测验得分 TT 基因型与 G 等位基因（GG+GT）携带者间差异均无统计学意义。结论 miR-137 基因 rs1625579 位点多态性可能与中国汉族人 群精神分裂症工作记忆能力有关.     

对氧磷酯酶基因多态性与糖尿病视网膜病变的关系(附236例分析)

目的 探讨对氧磷酯酶2(PON2)基因A148G多态性与糖尿病视网膜病变的关系。方法 (1)用聚合酶链反应—限制性片段长度多态性(PCR—RFLP)分析法探查PON2基因A148G多态性在正常对照组、单纯2型糖尿病组、糖尿病视网膜病变组中的基因分布频率；(2)放免法检测血清免疫反应性胰岛素(IRI)、C肽(C—P)水平。结果 (1)糖尿病视网膜病变组的GG基因型和G等位基因频率明显高于单纯2型糖尿病组(X^2＝3．98 P＜0.05，X^2＝4．49 P＜0.05)和正常对照组(X^2＝8．44 P＜0.01，X^2＝8．66 P＜0.01)；(2)方差分析结果显示基因型为GG的糖尿病患者空腹血糖浓度明显高于基因型为GA和AA的糖尿病患者(F＝3．94 P＜0.05，F＝5．17 P＜0.05)，而正常对照组各基因型间空腹血糖浓度无显著性差异(P＞0.05)；(3)非参数检验表明PON2基因多态性与糖尿病视网膜病变的发生有关(Z＝0．574 P＜0.05)，多因素分析结果表明PON2基因型(相对危险度为3．5471 P＜0．001，模型总判对率90．31％)和空腹血糖浓度(相对危险度为4．0143 P＜0．001，模型总判对率89．74％)与糖尿病视网膜病变独立相关。结论 PON2基因多态性与糖尿病视网膜病变有关，糖尿病视网膜病变的易感性在一定程度上与较高的空腹血糖浓度有关。