AIM:To evaluate the association between HLA-DRB1 alleles and Han and Uyghur ulcerative colitis (UC) patients residing in the Xinjiang Uyghur Autonomous Region of China. METHODS:In this study, 102 UC patients (53 Han i...AIM:To evaluate the association between HLA-DRB1 alleles and Han and Uyghur ulcerative colitis (UC) patients residing in the Xinjiang Uyghur Autonomous Region of China. METHODS:In this study, 102 UC patients (53 Han including 22 men and 31 women, and 49 Uyghur patients including 25 men and 24 women; aged 48.07 ± 15.83 years) and 310 age- and sex-matched healthy controls were enrolled in the Department of Gastroenterology, Xinjiang People's Hospital of China from January 2010 to May 2011. UC was diagnosed based on the clinical, endoscopic and histological findings following Lennard-Jones criteria. Blood samples were collected and genomic DNA was extracted by routine laboratory methods, and both polymerase chain reaction and gene sequencing were used to identify HLA-DRB1 allele variants. The potential association between genetic varia-tion and UC in Han and Uyghur patients was examined. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. RESULTS:There was no significant difference in the sex ratio between the controls and UC patients (P = 0.740). In Han patients with UC (n = 53), HLA-DRB1 *03 , *13 allele frequencies were lower than in healthy controls (n = 161), but not statistically significant, and HLA-DRB1*04*11*14 allele frequencies were higher than in healthy controls, but without statistical significance. Differences between Uyghur UC patients and the control group were observed for HLA-DRB1*04 and HLA-DRB1*13 , both showed a greater frequency in UC patients (10.21% vs 2.69%, P = 0.043; 14.29% vs 4.03%, P = 0.019). HLA-DRB1*14 also showed a greater frequency in UC patients (14.29% vs 2.69%, P = 0.006). The frequencies of DRB1*04 , *13*14 alleles were increased in Uyghur UC patients compared with normal controls. The frequency of DRB1 * 08 was decreased in Uyghur UC patients compared with normal controls. HLA-DRB1 alleles showed no association with UC in Han patients. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. The frequencies of DRB1*04 , *13*14 alleles were increased in Uyghur UC patients compared with normal controls. The frequency of DRB1*08 was decreased in Uyghur UC patients compared with normal controls. Polymorphism of the HLA-DRB1 gene may contribute to the clinical heterogeneity of UC between Han and Uyghur UC patients in China. CONCLUSION:HLA-DRB1*04*13*14 and DRB1*08 may contribute to the clinical heterogeneity of UC between Han and Uyghur UC patients.展开更多
Renal transplantation provides the best long-term treatment for chronic renal failure. Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases....Renal transplantation provides the best long-term treatment for chronic renal failure. Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases. Also, the genetics of human phenotype variation could be understood by knowing the functions of these SNPs. It is still a major challenge to identify the functional SNPs in a disease-related gene. This work explored how SNPs mutations in HLA-DRB1 gene could affect renal transplantation rejection. This study was carried out in Ahmed Gasim Hospital, Renal Dialysis Center during the period, from September 2012 to November 2013. Blood samples from five Sudanese patients (different families) with known renal transplantation rejection were collected before hemodialysis, furthermore one blood sample for control. DNA sequences results and detected SNPs were analyzed using bioinformatics tools (BLAST, SIFT, nsSNP Analyzer, PolyPhen, I-mutant, BioEdit, CPH, Chimera, Box shade and Project Hope). In addition, international databases were used for datasets [NCBI, Uniprot]. Results showed that, three SNPs were detected;two of three SNPs were predicted as tolerant or benign (rs1059575, novel) and one was deleterious (rs17885437). This study concluded that the identification of pathological SNPs could be an answer to unknown causes for a lot of organ transplantation rejection cases.展开更多
目的:研究子痫前期患者发病机制中相关的免疫学变化及基因背景。方法:SAP法检测血液中NK细胞数量。MTT珐检测NK细胞增殖能力。51Cr释放法测定NK细胞杀伤活性。免疫组化法检测胎盘蜕膜浸润的NK细胞数量及HLA-G蛋白表达水平。RT-PCR和real...目的:研究子痫前期患者发病机制中相关的免疫学变化及基因背景。方法:SAP法检测血液中NK细胞数量。MTT珐检测NK细胞增殖能力。51Cr释放法测定NK细胞杀伤活性。免疫组化法检测胎盘蜕膜浸润的NK细胞数量及HLA-G蛋白表达水平。RT-PCR和real time PCR法检测胎盘蜕膜组织HLA-G mRNA。PCR-SSP法检测两组HLA-DRB1等位基因频率,并分析母/儿间所携带某些HLA-DRB1等位基因配伍的频率。结果:①子痫前期患者外周血及其新生儿脐血NK细胞数均显著高于正常晚孕者及其新生儿。②子痫前期患者外周血及其新生儿脐血NK细胞增殖活性及杀伤活性均明显高于正常晚孕组(P<0.05)。③轻度与重度子痫前期组胎盘蜕膜NK细胞均多于正常晚孕组,但仅重度子痫前期组蜕膜NK细胞数量增加有统计学意义(P<0.05)。④轻度子痫前期组、重度子痫前期组和正常晚孕组之间HLA-G mRNA水平两两比较差异均无统计学意义(P>0.05)。⑤轻度子痫前期组HLA-G蛋白表达水平与正常晚孕组无显著性差异,重度子痫前期组胎盘HLA-G蛋白表达水平较正常晚孕组显著降低(P<0.05)。⑥两组孕妇和新生儿均检出13个HLA-DRB1等位基因,各等位基因频率在两组间均无明显差异。子痫前期组母不携带HLA-DRB1*04基因/儿携带DRB1*04基因、均不携带HLA-DRB1*14基因的频率显著高于正常晚孕组(P<0.05);母/儿均不携带HLA-DRB1*10基因、均携带HLA-DRB1*14的频率显著低于正常晚孕组(P<0.05)。结论:①先兆子痫患者外周血、脐血及蜕膜的NK细胞数量增多,活性增强,在妊娠过程中影响母胎免疫耐受。②母婴所携带的某些HLA-DRB1基因配伍与子痫前期易感性或抗性相关;父源性HLA-DRB1*04基因与子痫前期易感性相关。展开更多
基金Supported by Natural Science Foundation of Xinjiang Uyghur Autonomous Region of China,No.2009211A26
文摘AIM:To evaluate the association between HLA-DRB1 alleles and Han and Uyghur ulcerative colitis (UC) patients residing in the Xinjiang Uyghur Autonomous Region of China. METHODS:In this study, 102 UC patients (53 Han including 22 men and 31 women, and 49 Uyghur patients including 25 men and 24 women; aged 48.07 ± 15.83 years) and 310 age- and sex-matched healthy controls were enrolled in the Department of Gastroenterology, Xinjiang People's Hospital of China from January 2010 to May 2011. UC was diagnosed based on the clinical, endoscopic and histological findings following Lennard-Jones criteria. Blood samples were collected and genomic DNA was extracted by routine laboratory methods, and both polymerase chain reaction and gene sequencing were used to identify HLA-DRB1 allele variants. The potential association between genetic varia-tion and UC in Han and Uyghur patients was examined. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. RESULTS:There was no significant difference in the sex ratio between the controls and UC patients (P = 0.740). In Han patients with UC (n = 53), HLA-DRB1 *03 , *13 allele frequencies were lower than in healthy controls (n = 161), but not statistically significant, and HLA-DRB1*04*11*14 allele frequencies were higher than in healthy controls, but without statistical significance. Differences between Uyghur UC patients and the control group were observed for HLA-DRB1*04 and HLA-DRB1*13 , both showed a greater frequency in UC patients (10.21% vs 2.69%, P = 0.043; 14.29% vs 4.03%, P = 0.019). HLA-DRB1*14 also showed a greater frequency in UC patients (14.29% vs 2.69%, P = 0.006). The frequencies of DRB1*04 , *13*14 alleles were increased in Uyghur UC patients compared with normal controls. The frequency of DRB1 * 08 was decreased in Uyghur UC patients compared with normal controls. HLA-DRB1 alleles showed no association with UC in Han patients. There were no statistical differences in HLA-DRB1 allele frequencies in Han UC patients. The frequencies of DRB1*04 , *13*14 alleles were increased in Uyghur UC patients compared with normal controls. The frequency of DRB1*08 was decreased in Uyghur UC patients compared with normal controls. Polymorphism of the HLA-DRB1 gene may contribute to the clinical heterogeneity of UC between Han and Uyghur UC patients in China. CONCLUSION:HLA-DRB1*04*13*14 and DRB1*08 may contribute to the clinical heterogeneity of UC between Han and Uyghur UC patients.
文摘Renal transplantation provides the best long-term treatment for chronic renal failure. Single-nucleotide polymorphisms (SNPs) play a major role in the understanding of the genetic basis of many complex human diseases. Also, the genetics of human phenotype variation could be understood by knowing the functions of these SNPs. It is still a major challenge to identify the functional SNPs in a disease-related gene. This work explored how SNPs mutations in HLA-DRB1 gene could affect renal transplantation rejection. This study was carried out in Ahmed Gasim Hospital, Renal Dialysis Center during the period, from September 2012 to November 2013. Blood samples from five Sudanese patients (different families) with known renal transplantation rejection were collected before hemodialysis, furthermore one blood sample for control. DNA sequences results and detected SNPs were analyzed using bioinformatics tools (BLAST, SIFT, nsSNP Analyzer, PolyPhen, I-mutant, BioEdit, CPH, Chimera, Box shade and Project Hope). In addition, international databases were used for datasets [NCBI, Uniprot]. Results showed that, three SNPs were detected;two of three SNPs were predicted as tolerant or benign (rs1059575, novel) and one was deleterious (rs17885437). This study concluded that the identification of pathological SNPs could be an answer to unknown causes for a lot of organ transplantation rejection cases.
文摘目的:研究子痫前期患者发病机制中相关的免疫学变化及基因背景。方法:SAP法检测血液中NK细胞数量。MTT珐检测NK细胞增殖能力。51Cr释放法测定NK细胞杀伤活性。免疫组化法检测胎盘蜕膜浸润的NK细胞数量及HLA-G蛋白表达水平。RT-PCR和real time PCR法检测胎盘蜕膜组织HLA-G mRNA。PCR-SSP法检测两组HLA-DRB1等位基因频率,并分析母/儿间所携带某些HLA-DRB1等位基因配伍的频率。结果:①子痫前期患者外周血及其新生儿脐血NK细胞数均显著高于正常晚孕者及其新生儿。②子痫前期患者外周血及其新生儿脐血NK细胞增殖活性及杀伤活性均明显高于正常晚孕组(P<0.05)。③轻度与重度子痫前期组胎盘蜕膜NK细胞均多于正常晚孕组,但仅重度子痫前期组蜕膜NK细胞数量增加有统计学意义(P<0.05)。④轻度子痫前期组、重度子痫前期组和正常晚孕组之间HLA-G mRNA水平两两比较差异均无统计学意义(P>0.05)。⑤轻度子痫前期组HLA-G蛋白表达水平与正常晚孕组无显著性差异,重度子痫前期组胎盘HLA-G蛋白表达水平较正常晚孕组显著降低(P<0.05)。⑥两组孕妇和新生儿均检出13个HLA-DRB1等位基因,各等位基因频率在两组间均无明显差异。子痫前期组母不携带HLA-DRB1*04基因/儿携带DRB1*04基因、均不携带HLA-DRB1*14基因的频率显著高于正常晚孕组(P<0.05);母/儿均不携带HLA-DRB1*10基因、均携带HLA-DRB1*14的频率显著低于正常晚孕组(P<0.05)。结论:①先兆子痫患者外周血、脐血及蜕膜的NK细胞数量增多,活性增强,在妊娠过程中影响母胎免疫耐受。②母婴所携带的某些HLA-DRB1基因配伍与子痫前期易感性或抗性相关;父源性HLA-DRB1*04基因与子痫前期易感性相关。
