CYP1182-344T/C基因多态性与2型糖尿病肾病的关系

目的:研究2型糖尿病(T2DM)患者CYPlIB2.344T/C基因多态性与糖尿病肾病(DN)的相关性以及与DN不同分期的关系.方法:将145例12DM患者分为DN组73例和糖尿病非肾病组(NDN组)72例,另选择52例门诊体验健康人为正常对照组(NC组).应用聚合酶链反应一限制性内切酶片段长度多态性(PCR-RFLP)对以上197例观察对象进行基因型分析.结果:(1)DN患者存在CYPllB2-344T/C多态性.本研究197例观察对象中CYP11B2-344T/C多态性存在CC、CT、TT3种基因型,频率分别为12.7%、50.3%、37.1%;C、T等位基因频率分别为31.2%、68.8%.(2)DN组CYPllB2.344T/C T等位基因频率明显高于NC组(P<0.05).(3)DN组CYP11B2-344T/C多态性CC、CT、TT3种基因型各临床指标均数比较差异无显著性(均P0.05).(4)DN组内微量白蛋白尿期、临床白蛋白尿期和肾功能不全期CC、TT、CT基因型频率和C、T等位基因频率差异均无显著性(均P0.05).(5)CYP11B2-344T/C基因型与DN无相关性(P0.05).(6)DN患者TT基因型血浆醛固酮水平最高.结论:CYP1182-344T/C多态性与2型糖尿病肾病无显著相关性.     

新疆哈萨克族、维吾尔族、汉族代谢综合征与CYP11B2基因-344T/C多态性相关性研究

目的:探讨新疆哈萨克、维吾尔、汉族不同人群醛固酮合成酶基因CYP11B2基因(-344)T/C多态性与代谢综合征(metabolic syndrome,MS)的关联性.方法:选取新疆哈萨克、维吾尔、汉族居民共1 220例,均用常规方法提取白细胞DNA.用PCR结合限制性内切酶(HaeⅢ)检测CYP11B2基因(-344)T/C多态性.根据有无MS分为MS组(汉族130例,哈萨克族115例,维吾尔族130例)和对照组(汉族206例,哈萨克族285例.维吾尔族354例).结果:(1)3个民族标化后MS的患病率明显不同(P<0.05).(2)3个民族CYP11B2-344T/C基因多态性CC、CT、TT基因型频率及等位基因分布频率相比较,差异有统计学意义(P<0.05).(3)维吾尔、哈萨克、汉3个民族CYP11B2-344T/C基因多态性CC、CT、TT基因型频率及等位基因分布频率分别与对照组比较,差异无统计学意义(P>0.05).结论:新疆地区维吾尔、哈萨克、汉族CYPllB2基因-344T/C多态性存在差异性,各民族内代谢综合征与CYP11B2基因-344T/C多态性无相关性.     

醛固酮合酶基因多态性与原发性高血压相关性研究

目的探讨醛固酮合酶基因(CYP11B2)-344T/C多态性与原发性高血压的相关性。方法采用关联分析,收集湖南地区汉族男性原发性高血压患者100例,正常对照100名。应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)对2组对象的CYP11B2-344T/C多态进行分析。结果2组对象CYP11B2基因型(TT型、CT型和CC型)的频率差异无统计学意义(χ2=0.34,P>0.05),等位基因的频率差异也无统计学意义(χ2=0.28,P>0.05),但各组内等位基因T的频率(原发性高血压组:67.67%)高于等位基因C(32.33%);对照组T69.67%高于C 30.33%。结论多基因联合分析显示,在男性患者中,CYP11B2-344T/C多态性与原发性高血压无明显相关,但CYP11B2-344各组内等位基因T的频率高于等位基因C。     

河北汉族人群醛固酮合成酶基因-344C/T多态性研究

目的对中国河北省正常人群CYP11B2基因-344C/T多态性分布特点进行初步研究。方法选取唐山市正常健康体检者,提取白细胞DNA,PCR扩增CYP11B片段,应用限制性内切酶HaeⅢ37℃酶切2h。酶切产物行25g/L琼脂糖凝胶电泳。紫外灯下观察基因型。结果CYP11B2基因-344C/T多态性在河北正常人群中分布是CC16.0%、CT41.7%、TT52.5%,C等位基因为26.8%,男女之间基因型、等位基因频率差异无统计学意义(P=0.544、0.382)。CYP11B2基因-344C/T多态性分布与日本、芬兰、南非、法国、德国、比利时等国正常人群分布存在显著性差异,不同种族之间差异有统计学意义(P<0.004)。结论不同种族、不同地区正常人群CYP11B2基因-344C/T多态性分布存在明显差异。     

EMILIN1 CYP11B2基因多态性与原发性高血压相关性研究

目的 研究 EMILIN1、CYP11B2基因多态性与原发性高血压的相关性。方法 回顾性分析该院2010年3月至2012年3月期间收治的100例原发性高血压患者,将其作为临床研究对象（患者组）,另选取血压正常的健康自愿者100例作为健康对照组,进行基因多态性的对比研究。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法 分别检测两组EMILIN1基因SNP位点和CYP11B2基因SNP位点的等位基因及基因型分布情况。结果 患者组患者EMILIN1基因rs2304682位点上的基因型与等位基因频率与健康对照组比较,差异有统计学意义（P＜0．05）,患者组CG基因型、G等位基因频率明显高于健康对照组,而CC基因型、C等位基因频率则比健康对照组低;CYP11B2基因多态性基因型及等位基因频率发现,患者组（CYP11B2）-344 T/C基因多态性中TT基因型、T基因频率明显高于健康对照组,而CT 基因型、C基因频率则低于健康对照组,差异均有统计学意义（P＜0．05）。结论 EMILIN1基因多态性可能与原发性高血压有一定的相关性,（CYP11B2）-344T/C位点上等位基因T的频率较高。     

醛固酮合酶基因多态性与原发性高血压相关性研究

目的探讨醛固酮合酶基因（CYP11B2）-344T/C多态性与原发性高血压的相关性。方法采用关联分析,收集湖南地区汉族男性原发性高血压患者100例,正常对照100名。应用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）对2组对象的CYP11B2-344T/C多态进行分析。结果2组对象CYP11B2基因型（TT型、CT型和CC型）的频率差异无统计学意义（χ^2=0.34,P〉0.05）,等位基因的频率差异也无统计学意义（χ^2=0.28,P〉0.05）,但各组内等位基因T的频率（原发性高血压组：67.67%）高于等位基因C（32.33%）;对照组T69.67%高于C 30.33%。结论多基因联合分析显示,在男性患者中,CYP11B2-344T/C多态性与原发性高血压无明显相关,但CYP11B2-344各组内等位基因T的频率高于等位基因C。     

北方汉族人群醛固酮合酶基因-344C/T多态性特点及与血压水平相关性

目的:分析北方汉族人群醛固酮合酶(CYP11B2)基因-344C/T多态性分布及与血压的相关性。方法:于2001-04/2002-09选取北京市、吉林省长春市、河北省唐山市和山东省成武县的健康体检者384例,均通过问诊没有任何器质性疾病史,临床和生化检查未发现有器质性疾病证据;均为汉族,没有任何血缘关系。受试者对研究内容知情同意。DNA提取并且通过聚合酶链反应技术结合限制性内切酶HaeⅢ聚合酶链反应产物酶切成功366例,应用限制性内切酶HaeⅢ37℃酶切2h。酶切产物25g/L琼脂糖凝胶电泳,紫外灯下观察基因型。结果:①CYP11B2基因-344C/T多态性在中国汉族人群中分布是CC7.9%、CT35.8%、TT56.3%,等位基因C25.8%、T74.2%。②CYP11B2基因-344C/T多态性分布与日本、芬兰、南非、法国、德国和比利时等国正常人群分布差异有显著性意义,不同种族之间差异有显著性意义(P<0.004)。③CYP11B2基因-344C/T多态性CC、CT和TT基因型之间收缩压、舒张压、脉压、平均动脉压差异无显著性意义(P>0.05)。结论:不同种族、不同地区正常人群CYP11B2基因-344C/T多态性分布存在明显差异,中国汉族人群血压水平与CYP11B2基因-344C/T多态性可能无关。     

吉林省地区朝鲜族和汉族健康人群醛固酮合酶基因（CYP11B2）-344T/C多态性分布的研究

目的分析我国吉林省地区朝鲜族和汉族健康人群醛固酮合酶基因（CYP11B2）-344T/C多态性的分布。方法应用聚合酶链反应（Polymerase Chain Reaction,PCR）和限制性片段长度多态性（Restriction Fragment LengthPolymorphism,RFLP）技术,对67名朝鲜族和59名汉族健康人群CYP11B2基因多态性进行检测,并比较基因型和等位基因频率的分布特征。结果 67名朝鲜族中CYP11B2基因CC、TC和TT基因型频率分别为9%（6/67）、22%（15/67）和69%（46/67）;59名汉族中CC、TC和TT基因型频率分别为19%（11/59）、27%（16/59）和54%（32/59）,两者差异无显著性（χ2=3.522;P=0.172）。朝鲜族人群C和T等位基因频率分别为20%和80%;汉族人群分别为32%和68%,两者差异具有显著性（χ2=4.763;P=0.029）。结论吉林省地区朝鲜族和汉族健康人群（CYP11B2）-344T/C基因型分布频率差异无显著性,朝鲜族健康人群T等位基因频率高于汉族。     

新疆哈萨克族人群内皮型一氧化氮合酶基因与醛固酮合成酶基因协同作用与原发性高血压的关联性

目的:分析新疆哈萨克族人群内皮型一氧化氮合酶(eNOS)基因与醛固酮合成酶CYP11B2T穴-344雪C基因协同作用与原发性高血压的关联性。方法:选择2001-01/2004-03在新疆巴里坤县普查的年龄≤60岁的哈萨克族牧民。原发性高血压组174例眼收缩压≥160mmHg(1mmHg=0.133kPa)和(或)舒张压≥95mmHg演,正常血压组157例眼收缩压<140mmHg和(或)舒张压<90mmHg演。所有受试者均测定血压,身高,体质量,总胆固醇,三酰甘油,空腹血糖。应用聚合酶链反应、限制性内切酶方法检测了CYP11B2基因C-344T及eNOS基因G894T多态性。结果:331例受试者均进入结果分析。①将CYP11B2T穴-344雪C基因型CC,CT,TT和eNOSG894T基因型GG,GT TT联合分为6组,结果显示:CYP11B2-344CC eNOS894GG基因型组合与CYP11B2-344CT eNOS894GG及CYP11B2-344TT eNOS894GT-TT比较,收缩压、舒张压较高(P<0.05雪,其他组合之间差异无显著性。②原发性高血压组CYP11B2-344CC eNOS894GG组合收缩压较CYP11B2-344TT eNOS894GG组合高(P<0.05),与其他组合之间差异无显著性,但收缩压及舒张压有高于其他基因型组合趋势。③正常血压组CYP11B2-344CC eNOS894GG组合与其他基因型组合之间比较,收缩压和舒张压无显著差异,但年龄较其他基因型组合大。结论:提示CYP11B2-344CC和eNOS894GG纯合子具有协同作用,可能与新疆哈萨克族高血压具有关联作用。     

AT1R 1166A/C和CYP11B2-344C/T基因多态性与湖南汉族原发性高血压的相关性

摘要：目的：探讨血管紧张素Ⅱ-1型受体（AT1R）1166A/C和醛固酮合酶（CYP11B2）-344T/C基因多态性与原发性高血压(EH)的相关性。 方法：用限制性片段长度多态性聚合酶链反应（PCR-RFLP）对100例EH患者和100例体检健康者AT1R 1166A/C和CYP11B2-344T/C基因多态性进行检测。 结果：EH组AT1R 1166A/C AC型和C等位基因的频率高于健康对照组;AC基因型的血压值、TG,TC,LDL-C均明显高于AA基因型。HDL-C低于AA型CYP11B2各基因型频率和等位基因频率无显著性差异（P＞0.05）。各组内等位基因T的频率高于等位基因C（P＜0.05）。两基因联合分析显示,相对于AA-TT联合基因型,同时携带AC-CT联合基因型的人群患高血压的危险性增加了2.25倍。 结论：AT1R 1166A/C多态性与EH易感性相关,CYP11B2-344T/C基因多态性与EH无关,携带T1R 1166A C型基因以及AC-CT联合基因型的人群患高血压的危险性大。     

Aldosterone synthase (CYP11B2)-344T/C polymorphism and renoprotective response to losartan treatment in diabetic nephropathy

OBJECTIVE: It has been suggested that an aldosterone synthase gene polymorphism (CYP11B2 -344T/C) is predictive of the blood pressure lowering effect of angiotensin II receptor blockers in essential hypertension. We investigated whether this polymorphism is predictive of reductions in blood pressure and albuminuria and preservation of glomerular filtration rate (GFR) during short-term and long-term treatment with losartan in 57 hypertensive type-1 diabetic patients with diabetic nephropathy. MATERIAL AND METHODS: After a 4-week washout period, patients received losartan (100 mg o.d.) and were followed for a mean follow-up of 36 months. At baseline, after 2 and 4 months, and every 6 months thereafter, GFR (51Cr-EDTA-clearance), albuminuria and 24-h blood pressure were determined. The CYP11B2 -344T/C polymorphism was determined by standard polymerase chain reaction (PCR). RESULTS: The TT, CT and CC genotypes were found in 28 %, 58 % and 14 % of patients, respectively. At baseline albuminuria and blood pressure did not differ between genotype groups. Plasma aldosterone levels (geometric mean (95 % CI)) were similar at baseline: 87 (60-125), 77 (53-112), and 89 (49-161) pg mL(-1) and during follow-up (not significant). After initiation of losartan treatment, comparable mean (SE) reductions in blood pressure and albuminuria were seen in patients with TT, CT and CC genotypes (p >0.6 between groups). After long-term follow-up, there was a tendency towards a difference in systolic blood pressure reduction (p = 0.07, one-way ANOVA), suggesting a poorer response in patients with the CC genotype. No significant difference in rate of decline in GFR (median (range)) was seen between groups (TT, CT, CC): 4.2 (-1.0 to 16.0), 3.2 (-1.6 to 13.8) and 2.6 (-0.1 to 11.0) mL min(-1)year(-1), respectively (p = 0.5). CONCLUSIONS: Compared to a previous smaller study of angiotensin II receptor blockade in essential hypertension, we could not confirm that CYP11B2 -344T/C genotypes contribute towards explaining the observed variability in response to treatment with angiotensin II receptor blockers, which could be due to lack of power.     

Association of the C-344T polymorphism of CYP11B2 gene with essential hypertension in Hani and Yi minorities of China

BACKGROUND: Aldosterone synthase (CYP11B2) is a key enzyme in the biosynthesis of aldosterone. Recently, a C-344T polymorphism in the promoter region of the CYP11B2 gene has been reported to be in association with high blood pressure. We investigated the association between this polymorphism and essential hypertension in Hani (n=305 individuals) and Yi (n=233 individuals) minorities of China. METHODS: CYP11B2 genotyping with polymerase chain reaction-restriction fragment length polymorphism was performed in 267 normotensive subjects and 271 essential hypertensive subjects. At the same time, the T(-344)C polymorphism detection in 33 subjects was also performed by sequencing. RESULT: The frequency of CYP11B2 C-344T genotype in normotensive controls and essential hypertensive cohort in Hani population were TT: 0.729 vs. 0.610; CT + CC: 0.271 vs. 0.390, respectively. The frequency of CYP11B2 C-344T genotype in normotensive controls and essential hypertensive cohort in Yi population were TT: 0.612 vs. 0.475; CT + CC: 0.388 vs. 0.525, respectively. The frequency of CC + CT genotype in the essential hypertensive group was significantly higher than that in the normotensive controls in both Hani and Yi populations (P<0.05). CONCLUSION: The -344C allele of the CYP11B2 may play a role in genetic predisposition to developing essential hypertension in Hani and Yi minorities of China.     

Aldosterone synthase (CYP11B2)­344T/C polymorphism and renoprotective response to losartan treatment in diabetic nephropathy

Objective. It has been suggested that an aldosterone synthase gene polymorphism (CYP11B2 ­344T/C) is predictive of the blood pressure lowering effect of angiotensin II receptor blockers in essential hypertension. We investigated whether this polymorphism is predictive of reductions in blood pressure and albuminuria and preservation of glomerular filtration rate (GFR) during short‐term and long‐term treatment with losartan in 57 hypertensive type‐1 diabetic patients with diabetic nephropathy. Material and methods. After a 4‐week washout period, patients received losartan (100 mg o.d.) and were followed for a mean follow‐up of 36 months. At baseline, after 2 and 4 months, and every 6 months thereafter, GFR (⁵¹Cr‐EDTA‐clearance), albuminuria and 24‐h blood pressure were determined. The CYP11B2 ­344T/C polymorphism was determined by standard polymerase chain reaction (PCR). Results. The TT, CT and CC genotypes were found in 28 %, 58 % and 14 % of patients, respectively. At baseline albuminuria and blood pressure did not differ between genotype groups. Plasma aldosterone levels (geometric mean (95 % CI)) were similar at baseline: 87 (60–125), 77 (53–112), and 89 (49–161) pg mL^?1 and during follow‐up (not significant). After initiation of losartan treatment, comparable mean (SE) reductions in blood pressure and albuminuria were seen in patients with TT, CT and CC genotypes (p >0.6 between groups). After long‐term follow‐up, there was a tendency towards a difference in systolic blood pressure reduction (p = 0.07, one‐way ANOVA), suggesting a poorer response in patients with the CC genotype. No significant difference in rate of decline in GFR (median (range)) was seen between groups (TT, CT, CC): 4.2 (?1.0 to 16.0), 3.2 (?1.6 to 13.8) and 2.6 (?0.1 to 11.0) mL min^?1year^?1, respectively (p = 0.5). Conclusions. Compared to a previous smaller study of angiotensin II receptor blockade in essential hypertension, we could not confirm that CYP11B2 ­344T/C genotypes contribute towards explaining the observed variability in response to treatment with angiotensin II receptor blockers, which could be due to lack of power.     

Phenotypic heterogeneity and associations of two aldose reductase gene polymorphisms with nephropathy and retinopathy in type 2 diabetes

OBJECTIVE: We investigated the phenotypic features of diabetic microvascular complications and their association with a (CA)(n) microsatellite and a C/T polymorphism at the 5' region of the aldose reductase gene (ALR2) in a consecutive cohort of 738 Chinese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Of the entire patient cohort, 392 were free of diabetes complications, or uncomplicated, 159 had diabetic nephropathy, 66 had diabetic retinopathy, and 121 had both diabetic nephropathy and retinopathy. Nephropathy was defined as urinary albumin excretion rate (AER) >or=20 micro g/min and albumin-to-creatinine ratio >or=3.5 mg/mmol in two urine collections. Retinopathy was defined by the presence of hemorrhages, exudates, laser marks, and fibrous proliferation or by a history of vitrectomy. (CA)(n) and C/T polymorphisms were examined by PCR followed by capillary electrophoresis and digestion with BfaI, respectively. RESULTS: In the whole cohort, patients with diabetic retinopathy (n = 187) had higher blood pressure and lower BMI, while those with diabetic nephropathy (n = 280) had higher blood pressure, waist-to-hip ratio, and lipid profile than those without the respective complications. The z+6 carriers of the (CA)(n) polymorphism were less common in patients with diabetic retinopathy than those without diabetic retinopathy (n = 551) (4.3 vs. 9.3%, P = 0.04). The CT/TT carriers had a higher AER than the CC carriers (30.2 x/divided by 7.2 vs. 21.9 x/divided by 6.9 micro g/min, P = 0.03). Further subgroup analysis was performed after excluding uncomplicated patients with <5 years disease duration. The group with both diabetic nephropathy and retinopathy had higher frequencies of the z-2 allele (25.7 vs. 16.9%, P = 0.03) and T allele (26.4 vs. 18.5%, P = 0.04) and a lower frequency of the z+6 allele (1.7 vs. 5.5%, P = 0.054) than the uncomplicated group. Multiple logistic regression analysis confirmed that z-2 carrying (odds ratio 2.6, 95% CI 1.20-5.83, P = 0.02) and CT/TT genotypes (OR 2.5, 95% CI 1.19-5.19, P = 0.02) were independent predictors for both diabetic nephropathy and retinopathy. CONCLUSIONS: Chinese type 2 diabetic patients exhibited phenotypic differences in terms of risk factors for both diabetic nephropathy and diabetic retinopathy. Both the z-2 allele of (CA)(n) polymorphism and T allele of ALR2 were independently associated with severe diabetic microvascular complications.     

AT1R基因、ACE基因和CYP基因多态性与妊娠期高血压疾病的相关性研究

目的 探讨血管紧张素Ⅱ-1型受体(AT1R)基因A1166-C、血管紧张素转换酶(ACE)基因插入/缺失(I/D)和醛固酮合成酶(CYP11B2)基因-344T/C位点多态性与妊娠期高血压疾病(HDCP)的相关关系.方法 采用聚合酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP),分别检测HDCP组86例和正常对照组175例AT1R基因A1166-C、ACE基因I/D和CYP11B2基因-344T/C突变位点的基因型.结果 HDCP组和正常对照组AT1R基因A1166-C、ACE基因I/D和CYPllB2基因-344T/C多态性18种组合的分布不同,构成比不同;这18种组合中,相对于AT1R-AA+ACE-Ⅱ+CYP 1182-TT基因型,携带AT1R-AA+ACE-DD+CYP11B2-TC基因型人群的OR值为7.289;携带AT1R-AC+ACE-ID+CYP11B2-TC基因型人群的OR值为5.315;携带AT1R.AC+ACE-DD+CYP11B2-TC基因型人群的OR值为5.694.其余联合基因型,差异均无统计学意义(P均0.05);或者由于样本量小,不具有代表性.结论 HDCP组和正常对照组AT1R基因A1166-C、ACE基因I/D和CYPllB2基因-344T/C多态性18种组合中,AT1R-AA+ACE-DD+CYP11B2-TC联合基因型、AT1R-AC+ACE-ID+CYP11B2-TC联合基因型、AT1R-AC+ACE-DD+CYP11B2-TC联合基因型可能增加HDCP的遗传易感性;HDCP的发生,可能是多个基因共同作用的结果 .     

2 型糖尿病肾病患者外周血E- 选择素表达水平及其基因G98T 和A561C 位点多态性与代谢指标的相关性研究

目的　探讨2 型糖尿病肾病（type 2 diabetic nephropathy）患者外周E- 选择素(E-selectin) 表达水平及其基因G98T 和A561C 位点多态性与代谢指标相关性。方法　选取陕西省人民医院2020 年9 月～ 2021 年10 月确诊的2 型糖尿病肾病患者203 例作为糖尿病肾病组。依据糖尿病肾病分期分为5 组:A Ⅰ组39 例,A Ⅱ组42 例,A Ⅲ组40 例,A Ⅳ组47 例,A Ⅴ组35 例,以同期40 例健康体检者为对照组。采用酶联免疫吸附法（ELISA 法）测定血清可溶性E- 选择素水平,聚合酶链反应- 限制性片段长度多态性(PCR-RFLP) 方法检测 E- 选择素G98T 和A561C 基因的基因型和等位基因,Pearson 相关性分析E- 选择素及基因多态性与2 型糖尿病肾病代谢指标的关系,多因素logisitic 回归分析影响2型糖尿病肾病严重性指标。结果　糖尿病肾病组E- 选择素水平（42.34±12.35μg/L）高于对照组（8.10±3.60μg/L）,差异有统计学意义（t=7.43, P ＜ 0.05）,且A Ⅰ～ A Ⅴ组E- 选择素水平随糖尿病肾病疾病严重程度增加而升高,差异有统计学意义（F=4.57,P ＜ 0.05）。糖尿病肾病组E- 选择素基因G98T 位点T 等位基因（20.70%）,A561C 位点C 等位基因（14.30%）频率明显高于对照组（7.50%,6.25%）,差异均有统计学意义（χ2=8.23, 6.44,均P ＜ 0.05）。Pearson 相关性分析结果显示E- 选择素水平、E- 选择素G98T 位点TT 基因型,A561C 位点CC 基因型与代谢指标（BUN,Cr,TG,TC,FPG,HbAlc,FINS,HOMA-IR）呈正相关（r=0.21 ～ 0.73, 均P ＜ 0.05）。多因素Logisitic 回归分析结果显示BUN, Cr, TG, TC ,FPG, HbAlc, FINS, HOMA-IR, E- 选择素水平及E- 选择素G98T 位点TT 基因型,A561C 位点CC 基因型均为2 型糖尿病肾病的独立危险因素（OR=1.13 ～ 1.94,均P ＜ 0.05）。结论　E- 选择素及其基因G98T 位点和A561C 位点多态性与代谢指标密切相关,是2 型糖尿病肾病的独立危险因素,可为2 型糖尿病肾病诊疗提供一定参考价值。     

Functional impact of CYP2C95, CYP2C96, CYP2C98, and CYP2C911 in vivo among black Africans

Background and aim Previous data indicate that the urinary losartan/E-3174 ratio is a marker for cytochrome P450 (CYP) 2C9 activity in vivo. The functional impact of CYP2C9*5, *6, *8, and *11 polymorphisms in vivo has not been investigated previously in humans. METHODS: A single oral dose of losartan (25 mg) was given to 19 Beninese subjects with CYP2C9*1/*1 (n = 9), *1/*5 (n = 1), *1/*6 (n = 1), *1/*8 (n = 2), *1/*11 (n = 3), *5/*6 (n = 1), *5/*8 (n = 1), and *8/*11 (n = 1) genotypes. Concentrations of losartan and its active metabolite E-3174 were determined in urine from 0 to 8 hours by HPLC. The losartan/E-3174 metabolic ratio was used as a measure of losartan oxidation in vivo. RESULTS: The urinary losartan/E-3174 ratio in the various genotypes was as follows: 1.85 +/- 2.4 (mean +/- SD) for CYP2C9*1/*1, 14.6 for CYP2C9*1/*5, 4.2 for CYP2C9*1/*6, 188 for CYP2C9*5/*6, 11.6 for CYP2C9*5/*8, 0.44 +/- 0.13 (mean +/- SD) for CYP2C9*1/*8, 2.2 for CYP2C9*8/*11, and 5.72 +/- 4.5 (mean +/- SD) for CYP2C9*1/*11. Compared with the CYP2C9*1/*1 genotypes, the losartan/E-3174 ratio was significantly different in the CYP2C9*5 allele carriers (CYP2C9*1/*5, CYP2C9*5/*8, and CYP2C9*5/*6 genotypes) (P =.01, Mann-Whitney) but was not different in CYP2C9*1/*8 (P =.16) and CYP2C9*1/*11 (P =.11) carriers. The urinary losartan/E-3174 ratio of the single CYP2C9*1/*6 subject was higher than the 95% confidence interval of the mean of the CYP2C9*1/*1 group (0.0-3.7), whereas the metabolic ratio of the CYP2C9*8/*11 carrier was inside the 95% confidence interval of the means of the CYP2C9*1/*1 and CYP2C9*1/*11 groups (0.0-18). CONCLUSIONS: The CYP2C9*5 and *6 alleles are associated with decreased enzyme activity in vivo compared with the wild-type variant, whereas the CYP2C9*8 and *11 variants did not appear to have large in vivo effects.     

Association of CYP2E1 and NAT2 gene polymorphisms with chronic obstructive pulmonary disease

BACKGROUND: Detoxification genes are potential candidates in the susceptibility of patients with chronic obstructive pulmonary disease. Polymorphisms in these genes alter the metabolism of xenobiotics such as present in cigarette smoke. METHODS: We conducted a case-control study to investigate total 9 polymorphisms of CYP2E1, CYP2D6 and NAT2 genes by PCR-RFLP. RESULTS: The -1053C/T and -1293G/C promoter polymorphisms of CYP2E1 were found to be in complete linkage disequilibrium (LD) (D'=1.00, r(2)=1.0, p<0.0001), whereas -1293G/C and 7632T/A polymorphisms of the same gene were also in significant LD (D'=0.5183, r(2)=1.0, p=0.01) in patients. The patients over-represented the -1293GC+CC genotypes of -1293G/C polymorphism of CYP2E1 (p=0.03) and NAT2*4/7, NAT2()5/6, NAT2*5/7, NAT2*6/6 and NAT2*6/7 genotypes of NAT2 (p=0.01, p=0.039, p=0.01, p=0.032, p=0.006, respectively), resulting in to higher frequency of -1293C (OR=7.02, 95% CI=1.63-30.15, p=0.002), NAT2*6 (OR=1.90, 95% CI=1.27-2.83, p=0.001) and NAT2*7 (OR=2.91, 95% CI=1.65-5.12, p=0.0001) alleles. The 7632T/A and 9893C/G polymorphisms of CYP2E1 and 1934G/A polymorphism of CYP2D6 did not associate with the disease (p>0.05). The haplotypes -1293G:9893C and -1293G:7632T:9893C were under-represented (p<0.001), whereas haplotypes -1293C:7632T, -1293C:9893C, -1293C:9893G and -1293C:7632T:9893C of the 4 CYP2E1 polymorphisms were over-represented in patients (p<0.05). CONCLUSION: The CYP2E1 and NAT2 variants associated with COPD.