一例前列腺癌P53基因第6外显子中的移码突变

以ＰＣＲ单链构象多态（ＰＣＲＳＳＣＰ）分析及ＰＣＲ直接测序技术，结合免疫组织化学方法，对１例前列腺癌患者治疗前的前列腺穿刺组织及内分泌治疗后复发的手术切除标本中不同部位随机取材的肿瘤组织进行Ｐ５３基因第５，６外显子及Ｐ５３蛋白表达的检测，发现在第６外显子的第２０８密码子存在碱基插入突变（ＧＡＣ→ＧＡＴ），免疫组织化学检测中未发现Ｐ５３蛋白的过量表达。前列腺癌中尚未见有此种Ｐ５３基因突变的文献报道。     

PCR-SSP及PCR-SSCP在骨髓移植配型中的联合应用

目的 研究ＨＬＡ抗原分型的方法。方法 对２０例已进行ＨＬＡ抗原血清学分型的骨髓移植供、受者采用序列特异引物聚合酶链反应（ＰＣＲ－ＳＳＰ）及单链构象多态性聚合酶链反应（ＰＣＲ－ＳＳＣＰ）进行ＨＬＡ抗原的基因分型。ＤＮＡ的提取采用快速盐析法。结果 基因分型结果与血清学分型一致者有１８对,基因分型能明确判定而血清学分型无法判断者有２对;ＰＣＲ－ＳＳＰ与ＰＣＲ－ＳＳＣＰ结果完全一致者有１９对;１对ＰＣＲ－     

卵巢早衰患者卵泡刺激素受体基因突变的初步研究

对１４例受试者的卵泡刺激素（ＦＳＨ）受体基因进行了测试。１４例包括４例正常对照；１个有４个同胞姊妹的家庭，其中２人为卵巢早衰（ＰＯＦ）患者；其余５例为ＰＯＦ病人，１例为先天性卵巢不发育患者。采用限制片段长度多态性（ＲＦＬＰ），聚合酶链反应（ＰＣＲ），单链构象多态性（ＳＳＣＰ）和基因测序方法对受试者ＦＳＨ受体基因的第１～４、９和１０外显子作了检测。ＲＦＬＰ分析提示一些非特异性的变异可见于１例正常对照以及其他个别受试者；ＰＣＲ法未能检出异常的基因片段；ＳＳＣＰ筛选出第１０Ｄ外显子片段恒定呈现三种类型的ＤＮＡ移动带；对其中１０例的片段基因测序，发现４例纯合子，３例杂合子的基因片段在９１９位置上的腺嘌呤（Ａ）改变为鸟嘌呤（Ｇ），氨基酸由苏氨酸变成丙氨酸，这一改变在患者和对照都可见，但反复实验证明与ＤＮＡ碱基序列的立体构形有明确相关，而其他变异则未见此现象。提示ＦＳＨ受体基因的外显子的变异在正常人群中是存在的。ＰＯＦ很可能是一种潜在的多基因遗传疾病，而非一个特定的碱基变异所至。     

地塞米松和川芎嗪对狼疮肾炎外周血单个核细胞白细胞介素12表达的影响

目的　探讨地塞米松、川芎嗪对活动期、静止期狼疮肾炎（ Ｌ Ｎ） 外周血单个核细胞（ Ｐ Ｂ Ｍ Ｃ） 白细胞介素１２（ Ｉ Ｌ１２） 表达的影响。方法　应用地塞米松（１０ － ５ ｍｏｌ／ Ｌ） ,川芎嗪（３３ μｇ／ｍｌ） 对 Ｌ Ｎ 患者 Ｐ Ｂ Ｍ Ｃ 培养,以正常人为对照,分别采用 Ｅ Ｌ Ｉ Ｓ Ａ 法和半定量 Ｒ Ｔ Ｐ Ｃ Ｒ 法检测细胞上清液及细胞 Ｉ Ｌ１２ 和 Ｉ Ｌ１２ Ｐ４０ ｍ Ｒ Ｎ Ａ 表达。结果 Ｌ Ｎ 活动期、静止期较正常对照组 Ｉ Ｌ１２ 蛋白、基因水平明显增高（ Ｐ ＜ ０ ．０１） 。地塞米松明显抑制狼疮肾炎 Ｐ Ｂ Ｍ Ｃ Ｉ Ｌ１２ 表达（ Ｐ ＜ ０ ．０１） ,而川芎嗪仅对活动期狼疮肾炎 Ｐ Ｂ Ｍ Ｃ Ｉ Ｌ１２ 表达抑制明显（ Ｐ ＜ ０ ．０５） ,两种药物对正常人对照 Ｉ Ｌ１２ 表达无明显抑制作用（ Ｐ ＞ ０ ．０５） 。结论　狼疮肾炎 Ｉ Ｌ１２ 表达水平增高,这与 Ｐ Ｂ Ｍ Ｃ 处于异常活化状态有关;地塞米松、川芎嗪下调狼疮肾炎 Ｉ Ｌ１２ 表达,提示它们通过免疫调节直接抑制了活化的狼疮肾炎 Ｐ Ｂ Ｍ Ｃ 表达 Ｉ Ｌ１２     

脑外伤急性期脑脊液中ACTH,皮质醇的含量变化及其临床意义

对３３例急性脑外伤病脑脊液（ＣＳＦ）中ＡＣＴＨ，皮质醇的含量进行放免测定，结果发现，脑外伤后４８小时，６～１０天ＣＳＦ中ＡＣＴＨ，皮质醇含量呈持续升高状态，与对照组相比有高度显著性差异（Ｐ＞０．００１）。伤后２～３周ＡＣＴＨ值仍在较高水平，皮质醇含量稍降低，但仍明显高于对照组（Ｐ＜０．０５），入院时ＧＣＳ＜８分者ＣＳＦ中ＡＣＴＨ含量高于ＧＣＳ＞８分者（Ｐ＜０．０５）；ＣＳＦ压力＞１９６１．４Ｐａ者     

大肠癌患者粪便中C-erbB-2扩增和p53突变的检测及临床意义

目的　建立大肠癌患者粪便 Ｃｅｒｂ Ｂ２ 扩增及ｐ５３ 突变的检测方法,探讨大肠癌的基因诊断的临床意义。 方法　以差异聚合酶链反应（ Ｐ Ｃ Ｒ） 、 Ｐ Ｃ Ｒ单链构象多态性分析（ Ｓ Ｓ Ｃ Ｐ） 银染技术,分别检测大肠癌患者粪便 Ｃｅｒｂ Ｂ２ 扩增及ｐ５３ 突变。 结果　１４ 例中查出 Ｃｅｒｂ Ｂ２ 扩增７ 例（５０ ％ ） ,ｐ５３ 突变８ 例（５７ ％ ） ,二基因联合检出１１ 例（７９ ％ ） 。２ 例粪便潜血试验（ Ｆ Ｏ Ｂ Ｔ） 阴性中,１ 例 Ｃｅｒｂ Ｂ２扩增及ｐ５３ 突变均阳性,另１ 例ｐ５３ 突变阳性。 结论　联合多基因检测能对大肠癌的基因诊断提供更多的帮助,粪便 Ｄ Ｎ Ａ 标本的 Ｃｅｒｂ Ｂ２ 扩增及ｐ５３ 突变分析可为筛查尚无出血或 Ｆ Ｏ Ｂ Ｔ 假阴性的大肠癌及大肠癌高危个体的一种新的有效手段。     

PCR-SSCP法检测小儿原发性肾病综合征载脂蛋白E基因多态性

目的探讨小儿原发性肾病综合征（ＮＳ）脂质代谢紊乱机制。方法测定了６８例小儿ＮＳ及１２０例健康对照组７项血脂指标，采用聚合酶链反应－单链构象多态性（ＰＣＲ－ＳＳＣＰ）技术检测其载脂蛋白Ｅ（ＡｐｏＥ）基因多态性。并采用ＳＤＳ－ＰＡＧＥ检测ＮＳ组尿蛋白类型。结果所有７项指标在携不同ＡｐｏＥ等位基因（Ａｐｏε２、Ａｐｏε３及Ａｐｏε４）的患儿之间均无显著性差异（Ｐ＞０．０５），而携Ａｐｏε３等位基因型的选择性蛋白尿（ＳＰＵ）组血总胆固醇（ＴＣ）、甘油三酯（ＴＧ）显著高于同型的非选择性蛋白尿组（ＮＳＰＵ）（Ｐ＜０．０５）。ＮＳＰＵ组的Ａｐｏε２等位基因频率显著高于健康儿童组（１２．９６％ｖｓ５．００％，Ｐ＜０．０５）。结论小儿原发性ＮＳ的脂质紊乱主要与其蛋白代谢异常有关而与ＡｐｏＥ基因多态性无明显关系。但携Ａｐｏε２等位基因的ＮＳＰＵ患儿有进行性肾脏损害的可能。     

膀胱癌组织中MTS1基因缺失及突变的研究

我们采用ＤＮＡ聚合酶链反应（ＰＣＲ）和单链构象多态性分析（ＳＳＣＰ）技术对４８例膀胱癌组织中多肿瘤抑制基因（ＭＴＳ１）第２外显子点突变及存在状态进行了研究,旨在探讨ＭＴＳ１基因改变与膀胱癌发生发展的关系。１．资料和方法：（１）标本：４８例原发性膀胱癌组织均取自我院病理存档的石蜡包埋标本,且病理证实均为移行上皮癌。其病理分级为：Ｇ１２０例,Ｇ２１４例,Ｇ３１４例。临床分期为：Ｔ１,２３２例,Ｔ３,４１６例。另选８例正常膀胱组织作为对照。（２）膀胱癌组织ＤＮＡ提取：按分子克隆方法进行。（３）ＰＣＲ：…     

逆转录病毒载体介导HSV—TK基因在膀胱癌细胞的表达和作用

应用基因工程技术构建了带ＨＳＶＴＫ基因的逆转录病毒重组体ｐＬＮＳＸＴＫ，磷酸钙沉淀法转染ＰＡ３１７细胞，建立了重组病毒的载体产生细胞系ＰＡ３１７／ＴＫ细胞。用病毒上清感染人的膀胱癌细胞株ＢＩＵ８７，Ｇ４１８筛选抗性克隆ＢＩＵ８７／ＴＫ细胞。提取ＰＡ３１７／ＴＫ和ＢＩＵ８７／ＴＫ细胞的ＤＮＡ，用ＤＩＧ标记检测证实整合了ＨＳＶＴＫ基因，在病毒上清用ＲＴＰＣＲ检测到目的基因的转录。转导ＨＳＶＴＫ基因的膀胱癌细胞获得对ＡＣＶ的化学敏感性，给予ＡＣＶ可有效地杀伤肿瘤细胞。     

肾病综合征患者心钠素与糖皮质激素的相互关系

糖皮质激素（ＧＣ）应用于肾病综合征（ＰＮＳ）已有近４０年历史。因人类心钠素（ＡＮＦ）基因的第二个内含子存在有ＧＣ特异性结合位点，故认为ＧＣ可能是参予ＡＮＦ调控的体液因素之一。我们研究通过动态观察ＰＮＳ患者使用ＧＣ的过程中，血浆心钠素（ＰＡＮＦ）、皮质醇（ＰＣＴＳ）、促肾上腺皮质激素（ＰＡＣＴＨ）的水平变化，探讨ＧＣ发挥效应可能的分子生物学机理。一、材料与方法１．病历选择：随机选择１９９５年９月～１９９６年３月在我科住院的ＰＮＳ的３６例（按１９９２年黄山第三届全国肾脏病学术会议标准），男２０例，女…     

Plasminogen activator inhibitor-1 gene polymorphism 4G/4G genotype and lupus nephritis in Chinese patients

BACKGROUND: Abnormal regulation in the coagulation and fibrinolytic system may play an important role in mediating glomerular damage in lupus nephritis. Indeed, glomerular thrombosis occurs frequently in lupus nephritis and predicts the future development of glomerular sclerosis. In the murine model of active lupus nephritis, plasminogen activator inhibitor-1 (PAI-1) gene was overexpressed throughout the kidney, both within the glomeruli and also in tubules and vessels. The level of PAI-1 expression in the tissues appeared to correlate with the progression of lupus nephritis. Recently, a single base pair insertion/deletion 4G/5G polymorphism of the PAI-1 gene has been identified and shown to alter plasma PAI-1 activity. This study was therefore conducted to determine the association of the 4G/5G polymorphism of the PAI-1 gene with the development and severity of lupus nephritis. METHODS: The PAI-1 gene polymorphism of 118 systemic lupus erythematosus (SLE) patients and 103 healthy controls who were gender and age matched was determined using standard polymerase chain reaction. PAI-1 genotype results were studied in relationship to the development and severity of lupus nephritis. RESULTS: Allele frequencies of 4G/5G allele were 0.59/0.41 in lupus patients and 0.59/0.41 in controls (P = 1.000). No significant difference was noted in the genotype distribution between SLE patients with and without nephritis. However, lupus nephritis patients with the 4G4G genotype showed significantly heavier proteinuria (5.0 vs. 3.7 g/day; P = 0.023) when compared with patients with 4G5G and 5G5G genotypes. Also, 73.3% patients with 4G4G had an activity index > or =8 versus 37.3% patients with 4G5G and 5G5G (P = 0.003). Extensive necrotizing lesions were seen in 51.7% patients with 4G4G as compared with 23.5% patients with 4G5G and 5G5G (P = 0.014). The association of the 4G4G gene polymorphism with a higher nephritis activity and more severe necrotizing lesions persisted when only class III and class IV nephritis patients were studied. On the other hand, no significant association was noted between the PAI-1 gene polymorphism and the chronicity of the nephritis. CONCLUSION: These findings suggest that the 4G/5G polymorphism of the PAI-1 gene is associated with the activity but not the chronicity of lupus nephritis. The presence of the 4G4G genotype does not increase the risk of developing SLE or lupus nephritis, but predicts the development of higher nephritis activity and more extensive necrotizing lesions.     

Fc gamma RIIa polymorphism: a susceptibility factor for immune complex-mediated lupus nephritis in Brazilian patients.

BACKGROUND: Fc gamma RIIa is a low affinity receptor that has two co-dominantly expressed alleles, R131 and H131, which differ in their ability to bind immunoglobulin G (IgG) subclasses. Cells expressing H131 bind more efficiently complexed IgG2 and IgG3 than those expressing the R131 variant. The Fc gamma RIIa polymorphism has been shown to be associated with lupus nephritis. Here we evaluated the relevance of Fc gamma RIIa gene polymorphism in the development of lupus immune complex (IC)-mediated nephritis by comparing the genotype and allelic distribution of this receptor in lupus nephritis to ethnically matched healthy controls in Brazilians. METHODS: 119 systemic lupus erythematosus (SLE) patients and 48 healthy volunteers were recruited. Fc gamma RIIa genotyping was performed by PCR with allele-specific primers to distinguish between the two allelic forms (H131 and R131). RESULTS: Comparison of Fc gamma RIIa genotypes distribution in SLE patients with nephritis and in controls showed a significant increase in Fc gamma RIIa-R131 homozygosity (P < or = 0.02). The genotype distribution in lupus nephritis (45% with Fc gamma RIIa-R/R131, 30% with H/R131 and 25% with H/H131) was distinct from that observed in controls (21% with Fc gamma RIIa-R/R131, 52% with H/R131 and 27% with H/H131). In contrast, there was no difference in the distribution of Fc gamma RIIa genotypes in lupus without nephritis and controls (P = 0.3). Reinforcing the relevance of Fc gamma RIIa polymorphism in IC-mediated nephritis, patients with renal failure had an over-representation of the R131 allele (70%) when compared with normal controls (47%) (P = 0.06). CONCLUSIONS: The skewed distribution of Fc gamma RIIa genotypes with the predominance of homozygous R/R131 genotype observed in lupus nephritis emphasizes its importance as a heritable risk factor for IC-mediated renal injury in Brazilian lupus patients.     

Association of an insertion polymorphism of angiotensin-converting enzyme gene with the activity of lupus nephritis

BACKGROUND: Lupus nephritis is a common manifestation of systemic lupus erythematosus (SLE). The pathogenesis of lupus nephritis has not been fully understood; however, immunological abnormalities have been considered in the development and activity of lupus nephritis. As angiotensin-converting enzyme (ACE) is implicated in various immunological phenomena, we investigated the correlation between insertion (I)/ deletion (D) polymorphism of the ACE gene and the activity of lupus nephritis. PATIENTS AND METHODS: Eighty-four patients with SLE and 100 healthy subjects were enrolled in this study. Following the extraction of genomic DNA from the peripheral blood, the ACE genotype was determined by the polymerase chain reaction. The patients were classified by the histological findings according to the WHO classification. In addition, the activity index and chronicity index were used to assess the severity of renal involvement. RESULTS: Individuals with II genotype showed a significantly increased activity of lupus nephritis. The allelic frequency was I/D = 0.84/0.16 in patients with WHO class IV renal lesions, and I/D = 0.36/0.64 in those with WHO class I lesions and 0.61/0.39 in patients with WHO class I or WHO class II. The difference in the allelic frequency between patients with WHO class IV and those with WHO class I or WHO class I + WHO class II was statistically significant (p = 0.00016 or p = 0.027, respectively). Moreover, lupus nephritis patients with II genotype showed significantly higher activity index than those with DD genotype (p = 0.0009). CONCLUSION: These results suggest that the insertion polymorphism of the ACE gene may correlate with the activity of lupus nephritis.     

Association of IRF5 gene polymorphisms and lupus nephritis in a Chinese population

Aim: Recently, several studies have provided convincing evidence that polymorphisms in the interferon regulatory factor 5 (IRF5) gene were significantly associated with systemic lupus erythematosus (SLE) in several populations. The aim of this study was to investigate the association between IRF5 and lupus nephritis in a Chinese cohort and analyze the relationship between the rs2004640 genotype and the clinical and pathological phenotypes of lupus nephritis. Methods: The IRF5 rs2004640 polymorphism in a cohort of 190 Chinese lupus nephritis patients and 182 healthy Chinese blood donors was analyzed. The polymorphism examined was genotyped using the TaqMan assay. Results: The IRF5 rs2004640 T allele was associated with the susceptibility to lupus nephritis (rs2004640 T, 41.6% in patients, 30.8% in healthy controls, odds ratio = 1.6, P = 0.002). It was also found that the Chinese population had a much lower minor allele frequency of rs2004640 than Western populations studied to date. In the present cohort, 30.8% individuals in the control group had the detrimental T allele, compared to frequencies in the range of 44–56% that exist in Western populations. No association was found between IRF5 rs2004640 and pathology, or clinical presentation of lupus nephritis in the Chinese cohort examined. Conclusion: The results suggested that the rs2004640 T allele was associated with susceptibility to lupus nephritis and that the IRF5 polymorphism analyzed did not seem to be implicated in the pathology and clinical manifestation of lupus nephritis in the Chinese population.     

Association of FCGR3B gene copy number variations and lupus nephritis in Henan Han populations

Objective To evaluate the copy number variation of FCGR3B gene in Henan Han systemic lupus erythematosus (SLE) patients and healthy controls, and explore the association between FCGR3B gene copy number variants (CNVs) and lupus nephritis (LN) susceptibility in Henan Han population. Methods FCGR3B CNVs was investigated in 142 SLE patients with nephritis, 187 SLE patients without nephritis and 328 healthy controls. A modified methodology based on competitive PCR named Multiplex AccuCopyTM Kit was used to detect FCGR3B copy number. Clinical and laboratory data were collected retrospectively from the medical record. Logistic regression analysis was used to determine the association of FCGR3B copy number variants with LN susceptibility. Rank correlation was used to determine the correlations between FCGE3B copy number variants and clinical phenotypes of LN. Results No significant difference was detected in the copy number variations of FCGR3B in different groups. Low copy number of FCGR3B was more commonly seen in patients with nephritis (P=0.042), and was a risk factor for LN (OR=2.059; 95% CI: 1.081-3.921; P=0.028). However, high copy number (＞2) had no effect on SLE patients without nephritis(OR=1.152; 95%CI: 0.711-1.866; P=0.565) and LN patients (OR=0.838; 95%CI: 0.529-1.329; P=0.454). There were no associations between FCGR3B copy number variants and clinical phenotypes and immunologic characteristics of LN. Conclusion The low copy number of FCGR3B is a risk factor for LN in Henan Han population.     

Association of mannan-binding lectin gene polymorphisms withprogression of severe lupus nephritis

Objective To investigate the association of single nucleotide polymorphisms (SNPs) of the mannan-binding lectin (MBL) gene with serum levels, development, progression and prognosis ofsevere lupus nephritis (LN). Methods A total of 107 severe lupus nephritis patients were enrolled in the study from January 2003 to October 2013. Integrated capillary electrophoresis was used to detect MBL gene polymorphism in peripheral blood DNA. ELISA was used to detect serum MBL concentration. Kaplan-Meier survival analysis was used to analyse the relationship of renal function, kidney prognosis with the gene polymorphism of rs11003125. Cox regression model analysis was used to identify possible risk factors of kidney prognosis. Results SNPs in rs11003125, rs7096206, rs7095891 and rs1800450 were found. The serum MBL concentration of patients with GG genotype in rs11003125 was higher than that with GC genotype, and both were higher than that with CC genotype (P＜0.01). Patients with SNP of rs11003125 had higher systolic blood pressure, diastolic blood pressure, mean arterial pressure, serum creatinine, urea nitrogen, 24 hours urinary protein, and lower glomerular filtration rate, shorter mean renal survival time (P＜0.05). Progressive severe LN patients had higher GC+CC (91.9% vs 75.7%, P＝0.041), CT+TT（32.4% vs 14.3%, P＝0.027） genotype frequencies at promoter rs11003125 and rs7095891, respectively, compared with that of non-progressive severe LN patients. Conclusions rs11003125, rs7096206 and rs1800450 polymorphisms of MBL gene are associated with lower serum MBL levels in severe LN patients. rs11003125 promoter polymorphisms of MBL gene may contribute to the onset severity, progression and prognosis of severe lupus nephritis.     

Effect of methylprednisolone pulse therapy in patients with lupus nephritis assessed by WHO morphologic classification

To determine indications for treatment with high-dose intravenous methylprednisolone pulse therapy in lupus nephritis, we retrospectively assessed the response to pulse therapy over oral prednisolone administration in 120 biopsy proven lupus nephritis patients according to WHO morphologic classification. In the pulse group, 1 g of methylprednisolone was administered on three consecutive days and oral steroid therapy (40-30 mg) was started. In many occasions in treating class III and IV-b, repeated pulse therapy was performed. In control oral prednisolone group, middle-dose steroid therapy (50-30 mg) was started. In patients with minor glomerular abnormalities and mesangial lupus nephritis, rapid improvement of serological activities was observed in pulse group assessed by serum complement level, anti-DNA antibodies, and anti-nuclear antibodies. In patients with focal lupus nephritis, rapid rise in serum complement level and fall in proteinuria was observed in the pulse group. In patients with diffuse proliferative lupus nephritis with active necrotizing lesions, faster rise in serum complement level and proteinuria were observed in the pulse group. In patients with membranous lupus nephritis there was no significant difference between two groups. In comparison with the effect of pulse therapy among each morphologic class, the rise of serum complement level was slowest in class IV-b. Both group of IV-b and V manifested nephrotic syndrome and by pulse therapy the decrease in urinary protein was faster and more significant in class IV-b compared with class V. No significant adverse effect of methylprednisolone was observed during about 150 times of pulse therapy. Bacterial, viral infections such as herpes zoster and fungal infections were observed in pulse group as often as control group.     

T and B lymphocyte function in patients with lupus nephritis: correlation with renal pathology

The relationship between in vitro measures of T and B cell responses of peripheral blood lymphocytes and histological findings on renal biopsy was examined in 32 patients with lupus nephritis. T cell mediated responses, assessed by mixed leucocyte reaction (MLR) and cell mediated lympholysis (CML), were decreased, while spontaneous immunoglobulin secretion by B cells, measured by plaque forming cell (PFC) assay, was increased above normal in the whole patient population. There were no significant differences in these T or B cell responses between patients with the diffuse proliferative and the membranous forms of lupus nephritis. Using a semi-quantitative index of the histologic activity of diffuse proliferative lupus nephritis, a good correlation was noted between the degree of abnormality of B cell responses and the level of activity seen on renal biopsy. The nature of the relationship between B cell abnormalities and the expression of lupus nephritis warrants further study.     

Sex differences in estrogen receptor gene polymorphism and its association with lupus nephritis in Chinese

BACKGROUND/AIMS: Lupus nephritis (LN) is a clinical heterogeneous autoimmune disease and genetic factors contribute to the development of LN. One of the most striking characteristics in LN is the high prevalence among childbearing women, as well as that its clinical manifestation differs in women and men, suggesting the role of sex hormones in its pathogenesis. METHODS: The PvuII and XbaI restriction fragment length polymorphism (RFLP) of estrogen receptor (ER) gene were analyzed in 245 biopsy-proven LN patients (58 males and 187 females) and 172 normal controls (101 males and 71 females) by PCR-RFLP. The clinical and pathological features of 49 male and 152 female LN patients with different genotypes were analyzed. RESULTS: It was found that genotype PpXx, ppxx and Ppxx were three major genotypes of ER gene in both of lupus patients and control groups. The distribution of ER gene polymorphism was quite different in lupus patients of different genders. The frequency of the PpXx genotype in male LN patients was significantly higher than both the gender matched normal controls (p < 0.05) and the female LN patients (p < 0.05), while no difference was shown in the frequency of PpXx genotype between female LN patients and gender matched controls. Interestingly, skin rashes and arthritis were found more common in the patients with PpXx genotype. The frequency of hematological abnormalities and hypertension were higher in patients with ppxx genotype (p < 0.05), while capillary thrombi and glomerular sclerosis were more frequently complicated in the patients with ppxx genotype. In addition, the renal vasculitis and interstitial injury were more frequent in those with Ppxx genotype (p < 0.01). CONCLUSION: The distribution of ER gene polymorphism in LN patients is distinct with different gender. The PpXx genotype of ER gene may be associated with the susceptibility of SLE in male. ER gene polymorphism is probably one of the genetic factors contributing to the development of clinical heterogeneity and sexually dimorphic manifestations of LN.     

No association between a genetic variant of the p22(phox) component of NAD(P)H oxidase and the incidence and progression of IgA nephropathy.

BACKGROUND: The course of glomerulonephritis varies even within the same histological entity, which suggest that genetic factors determine the progression of inflammatory renal diseases. We studied a potential relationship between the C242T gene polymorphism of p22(phox), a subunit of the NAD(P)H oxidase, and frequency as well as progression of immunoglobulin A (IgA) nephropathy. Patients with lupus nephritis were also investigated. The distribution of the C242T gene variation of p22(phox) has not been previously studied in patients with renal disease. METHODS: Patients with IgA nephropathy were from a homogenous ethnic group of patients living in Northern Germany (n=127). Patients with active lupus nephritis WHO classes III/IV (n=46) were also studied. All diagnoses were confirmed by renal biopsy. Healthy blood donors (n=151) exhibited a genotype distribution similar to previously reported values for Caucasians (CC, 41.2%; CT, 45%; TT, 13.8%). However, C242T genotype distribution was not significantly different (chi(2) test) in patients with IgA nephropathy (CC, 44.9%; CT, 48%; TT, 7.1%) or in active lupus nephritis (CC, 54.3%; CT, 34.7%; TT, 11%). Grouping of IgA nephropathy patients as those with mild renal impairment at the time of biopsy (serum creatinine <1.3 mg/dl) and those with more severe renal failure (serum creatinine >1.3 mg/dl) also failed to show a relationship with p22(phox) polymorphism. Log-rank analysis for up to 15 years in selected cases of IgA nephropathy did not show a significant difference in renal survival rate among the three genotypes. CONCLUSIONS: It appears that the C242T polymorphism is not associated with IgA nephropathy or active lupus nephritis and may not affect the progressive deterioration of renal function in patients with IgA nephropathy. However, whether the C242T polymorphism plays a role in other renal diseases remains to be studied.