两个单核苷酸多态位点与北方中国人前列腺癌的关联研究

背景与目的:近年来在不同人群的研究中,全基因组关联研究已经发现了许多与前列腺癌(prostate cancer,PCa)风险相关的单核苷酸多态性位点(single nucleotide polymorphisms,SNPs).本文探讨了两个SNPs,即rs17021918 (4q22)与rs 10090154 (8q24)和中国北方汉族人PCa的相关性.方法:采用病例对照的研究方法,本研究入选了124例PCa患者和111例健康对照者,采用聚合酶链反应-高分辨熔解曲线(PCRHRM)技术,并结合测序验证法,对rs17021918(4q22)与rs10090154 (8q24)进行基因型及等位基因频率的分析,并探讨其与确诊时的体重指数(body mass index,BMI)、Gleason评分、血清前列腺特异性抗原(prostate specific antigen,PSA)水平、肿瘤分期及年龄等临床特征之间的联系.结果:在风险等位基因、基因型及分层分析中,rs17021918虽然并未观察到有统计学意义的结果,但风险比(the odds ratio,OR)值多＜1,其中在BMI＞27.5 kg/m2(P=0.056; OR=0.292; 95％CI:0.078～1.095)和PSA浓度＜10.0 ng/mL组(P=0.068;OR=0.467; 95％CI:0.204～1.069),CC基因型携带者可能有较低的PCa发病风险;另外发现,rs10090154的T等位基因携带者与较低的肿瘤分期关联(P=0.012; OR=2.512; 95％CI:1.210～5.214),而在较高的肿瘤分期组,T等位基因携带者与非T等位基因携带者之间差异有统计学意义(P=0.039).结论:Rs17021918的CC基因型携带者可能与中国北方人PCa发病风险负关联;而rs10090154的T等位基因携带者可能与中国北方人PCa肿瘤分期正关联.     

慢性肾病及相关并发症治疗药物研究进展

慢性肾病(chronic kidney disease, CKD)是一种伴随着多种并发症(心血管疾病、代谢性酸中毒和贫血等)的进行性疾病,在人群中有着较高的发病率和死亡率。目前的主要治疗药物包括肾素-血管紧张素-醛固酮通路抑制剂及钠-葡萄糖共转运蛋白2抑制剂,都只能延缓CKD向终末期肾病的进展,而不能彻底治疗CKD。随着更多在CKD进展中起到关键作用的通路被发现,新的有前景的治疗方法也有望被研发出来。本文对CKD和其并发症的主要疗法及新兴疗法进行了总结,以期为CKD新疗法的研发提供支持。     

整合素α6、β-微精浆蛋白基因和染色体8q24区与前列腺癌的关联研究

目的 探讨整合素α6(ITGA6)基因(rs12621278,G)、染色体8q24区(rs10086908,T)和β-微精浆蛋白(MSMB)基因(rs10993994,T)与北京市居民中前列腺癌(PCa)的关联,了解PCa患者基因型和表型的关系.方法 收集112例PCa患者临床、遗传、膳食习惯、嗜好等表型,对PCa患者和91名正常对照者的ITGA6基因(rs12621278,G)、染色体8q24区(rs10086908,T)和MSMB基因(rs10993994,T)进行比较,并进行病例组的基因型-表型分析.结果 2组间相比,MSMB基因rs10993994,T风险等位基因频率差异有统计学意义(病例组56.4%,对照组46.2%;P=0.001,OR=1.97,95%CI为1.28～3.04).8q24区的rs10086908,T(病例组83.5%,对照组79.2%)和ITGA6基因的rs12621278,G(病例组27.2%,对照组27.0%)组间差异无统计学意义(P＞0.05).数量性状分析发现ITGA6风险基因型(G/G)的患者病程为(1.40±0.55)年,显著短于A/G型的(4.38±3.10)年和A/A型的(2.37±1.84)年(P=0.003).结论 MSMB基因变异和PCa易感性之间存在相关性,提示MSMB基因可能与PCa有关联.

Abstract：

Objective To explore the correlation between ITGA6 gene (rs12621278, G), MSMB gene (rs10993994, T), chromosome 8q24 (rs10086908, T) and prostate cancer (PCa) in Beijing residents, and to explore the correlation between genotype and phenotype in PCa patients. Methods PCa patient phenotypes were collected including clinical, genetic, dietary habits, hobbies and blood samples. ITGA6 gene (rs12621278, G), chromosome 8q24 (rs10086908, T) and MSMB gene (rs10993994, T) compared the allele distribution between 112 PCa and 91 healthy control age matched patients. The genotype and phenotype analysis was conducted in the 2 groups. Results Between the case and control groups, only rs10993994, T of MSMB gene (case 56.4%,control 46.2%) was significantly different (P=0.001; OR=1.97, 95%CI:1.28-3.04). The rs10086908, T of 8q24 (case 83.5%, control 79.2%) and rs12621278, G of ITGA6 gene (case 27.2%, control 27.0%) were not significantly associated with PCa in the study sample (P>0.05). Quantitative trait analysis showed that the disease duration of ITGA6 risk genotypes (G/G,1.40±0.55 years) in PCa patients was significantly shorter (P=0.003) than the other genotype carriers (A/G, 4.38±3.10 years; A/A, 2.37±1.84 years). Conclusion The genetic variation in MSMB is possibly associated with PCa susceptibility, suggesting that MSMB genes might be associated with PCa in a Chinese population.