AIM:To investigate the contribution of fucosyltransferase 2 (FUT2) variants to the genetic susceptibility and clinical heterogeneity of ulcerative colitis (UC) between Han and Uyghur patients in Xinjiang, China. METHO...AIM:To investigate the contribution of fucosyltransferase 2 (FUT2) variants to the genetic susceptibility and clinical heterogeneity of ulcerative colitis (UC) between Han and Uyghur patients in Xinjiang, China. METHODS:A total of 102 UC patients (53 Han patients including 22 men and 31 women, and 49 Uyghur patients including 25 men and 24 women; aged 48 ± 16 years) and 310 age-and sex-matched healthy controls were enrolled from January 2010 to May 2011 in Xinjiang People's Hospital of China. 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 the routine laboratory methods. Polymerase chain reaction-sequence-based typing method was used to identify FUT2 variants rs281377, rs1047781, rs601338 and rs602662. Genotypic and allelic frequencies were documented and compared between the UC patients and the healthy controls. Genotypic frequencies were also compared between Han and Uyghur patients. Potential association of genetic variation and UC between Han and Uyghur patients was examined. RESULTS: rs281377 was found significantly associated with UC in the Han population as compared with the controls (P = 0.011) while rs281377 was not associated with UC in the Uyghur population (P = 0.06). TT homozygous rs281377 frequencies were higher in the UC groups than in the controls (88.7% vs 68.7% and 55.1% vs 50.3%). rs1047781 was specifically associated with UC in the Uyghur population (P = 0.001), but not associated with UC in the Han population (P = 0.13). TT homozygous rs1047781 frequencies were lower in the UC groups than in the controls (9.5% vs 11.8% and 4.0% vs 6.7%). rs601338 was statistically related to UC in both populations (Han, P = 0.025; Uyghur, P = 8.33 × 10 -5 ). AA homozygous rs601338 frequencies were lower in the UC groups than in the controls (0% vs 1.8% and 12.2% vs 13.4%). No association was found between rs602662 and UC in both Han and the Uyghur populations. Allelic analysis showed that rs281377 allele was significantly associated with UC in the Han population as compared with the controls [P = 0.001, odd ratio (OR) = 0.26], however, it was not associated with UC in the Uyghur population (P = 0.603, OR = 1.14), and rs1047781 allele was associated with UC in the Uyghur population (P = 0.001, OR = 0.029) while it was not associated with UC in the Han population (P = 0.074, OR = 0.62). Moreover, rs601338 was associated with UC in both Han (P = 0.005, OR = 0.1) and Uyghur pop- ulations (P = 0.002, OR = 0.43). Meta analysis showed that rs1047781 and rs601338 conferred risk of UC as compared with the controls [P = 0.005, OR = 0.47; P = 0.0003, OR = 0.35; 95% confidence interval (CI) = 0.31-0.72 and 0.21-0.58], but rs281377 and rs602662 showed no statistically significant differences betweenpatients with UC and controls (P = 0.10, OR = 0.71; P = 0.68, OR = 0.09; 95% CI = 0.47-1.07 and 0.56-1.47). CONCLUSION:Functionally relevant FUT2 gene variants are associated with UC, suggesting that they play a potential role in the pathogenesis of UC and may contribute to the clinical heterogeneity of UC between Han and Uyghur patients.展开更多
Glycosylation is a common post-translational modification in eukaryotic cells.It is involved in the production of many biologically active glycoproteins and the regulation of protein structure and function.Core fucosy...Glycosylation is a common post-translational modification in eukaryotic cells.It is involved in the production of many biologically active glycoproteins and the regulation of protein structure and function.Core fucosylation plays a vital role in the immune response.Most immune system molecules are core fucosylated glycoproteins such as complements,cluster differentiation antigens,immunoglobulins,cytokines,major histocompatibility complex molecules,adhesion molecules,and immune molecule synthesis-related transcription factors.These core fucosylated glycoproteins play important roles in antigen recognition and clearance,cell adhesion,lymphocyte activation,apoptosis,signal transduction,and endocytosis.Core fucosylation is dominated by fucosyltransferase 8(Fut8),which catalyzes the addition ofα-1,6-fucose to the innermost GlcNAc residue of N-glycans.Fut8 is involved in humoral,cellular,and mucosal immunity.Tumor immunology is associated with aberrant core fucosylation.Here,we summarize the roles and potential modulatory mechanisms of Fut8 in various immune processes of the gastrointestinal system.展开更多
本文介绍了阶段特异性胚胎抗原(stage specific embryonic antigen,SSEA)的发现、化学结构和在胚胎、成熟组织中的分布规律;SSEA通过参与细胞间的信息传递、细胞识别与粘附等过程在动物胚胎发育、组织分化、基因调控及肿瘤的发生、转移...本文介绍了阶段特异性胚胎抗原(stage specific embryonic antigen,SSEA)的发现、化学结构和在胚胎、成熟组织中的分布规律;SSEA通过参与细胞间的信息传递、细胞识别与粘附等过程在动物胚胎发育、组织分化、基因调控及肿瘤的发生、转移等方面发挥重要作用;SSEA作为细胞表面标志,在肿瘤患者确诊、预后监测及胚胎干细胞的分离纯化、鉴定等研究领域的重要应用价值;探讨了SSEA-1合成的关键酶——岩藻糖基转移酶基因表达与调控的研究进展。展开更多
基金Supported by National Natural Science Foundation of China,No. 30871148 and No. 81160052Natural Science Foundation of Xinjiang Uyghur Autonomous Region of China, No.2009211A26
文摘AIM:To investigate the contribution of fucosyltransferase 2 (FUT2) variants to the genetic susceptibility and clinical heterogeneity of ulcerative colitis (UC) between Han and Uyghur patients in Xinjiang, China. METHODS:A total of 102 UC patients (53 Han patients including 22 men and 31 women, and 49 Uyghur patients including 25 men and 24 women; aged 48 ± 16 years) and 310 age-and sex-matched healthy controls were enrolled from January 2010 to May 2011 in Xinjiang People's Hospital of China. 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 the routine laboratory methods. Polymerase chain reaction-sequence-based typing method was used to identify FUT2 variants rs281377, rs1047781, rs601338 and rs602662. Genotypic and allelic frequencies were documented and compared between the UC patients and the healthy controls. Genotypic frequencies were also compared between Han and Uyghur patients. Potential association of genetic variation and UC between Han and Uyghur patients was examined. RESULTS: rs281377 was found significantly associated with UC in the Han population as compared with the controls (P = 0.011) while rs281377 was not associated with UC in the Uyghur population (P = 0.06). TT homozygous rs281377 frequencies were higher in the UC groups than in the controls (88.7% vs 68.7% and 55.1% vs 50.3%). rs1047781 was specifically associated with UC in the Uyghur population (P = 0.001), but not associated with UC in the Han population (P = 0.13). TT homozygous rs1047781 frequencies were lower in the UC groups than in the controls (9.5% vs 11.8% and 4.0% vs 6.7%). rs601338 was statistically related to UC in both populations (Han, P = 0.025; Uyghur, P = 8.33 × 10 -5 ). AA homozygous rs601338 frequencies were lower in the UC groups than in the controls (0% vs 1.8% and 12.2% vs 13.4%). No association was found between rs602662 and UC in both Han and the Uyghur populations. Allelic analysis showed that rs281377 allele was significantly associated with UC in the Han population as compared with the controls [P = 0.001, odd ratio (OR) = 0.26], however, it was not associated with UC in the Uyghur population (P = 0.603, OR = 1.14), and rs1047781 allele was associated with UC in the Uyghur population (P = 0.001, OR = 0.029) while it was not associated with UC in the Han population (P = 0.074, OR = 0.62). Moreover, rs601338 was associated with UC in both Han (P = 0.005, OR = 0.1) and Uyghur pop- ulations (P = 0.002, OR = 0.43). Meta analysis showed that rs1047781 and rs601338 conferred risk of UC as compared with the controls [P = 0.005, OR = 0.47; P = 0.0003, OR = 0.35; 95% confidence interval (CI) = 0.31-0.72 and 0.21-0.58], but rs281377 and rs602662 showed no statistically significant differences betweenpatients with UC and controls (P = 0.10, OR = 0.71; P = 0.68, OR = 0.09; 95% CI = 0.47-1.07 and 0.56-1.47). CONCLUSION:Functionally relevant FUT2 gene variants are associated with UC, suggesting that they play a potential role in the pathogenesis of UC and may contribute to the clinical heterogeneity of UC between Han and Uyghur patients.
基金Supported by the National Natural Science Foundation of China,No.32171279Natural Science Foundation of Liaoning Province,No.2022-BS-254,and No.2022-MS-317the Project of Dalian Medical Science Research,No.2012026.
文摘Glycosylation is a common post-translational modification in eukaryotic cells.It is involved in the production of many biologically active glycoproteins and the regulation of protein structure and function.Core fucosylation plays a vital role in the immune response.Most immune system molecules are core fucosylated glycoproteins such as complements,cluster differentiation antigens,immunoglobulins,cytokines,major histocompatibility complex molecules,adhesion molecules,and immune molecule synthesis-related transcription factors.These core fucosylated glycoproteins play important roles in antigen recognition and clearance,cell adhesion,lymphocyte activation,apoptosis,signal transduction,and endocytosis.Core fucosylation is dominated by fucosyltransferase 8(Fut8),which catalyzes the addition ofα-1,6-fucose to the innermost GlcNAc residue of N-glycans.Fut8 is involved in humoral,cellular,and mucosal immunity.Tumor immunology is associated with aberrant core fucosylation.Here,we summarize the roles and potential modulatory mechanisms of Fut8 in various immune processes of the gastrointestinal system.
文摘本文介绍了阶段特异性胚胎抗原(stage specific embryonic antigen,SSEA)的发现、化学结构和在胚胎、成熟组织中的分布规律;SSEA通过参与细胞间的信息传递、细胞识别与粘附等过程在动物胚胎发育、组织分化、基因调控及肿瘤的发生、转移等方面发挥重要作用;SSEA作为细胞表面标志,在肿瘤患者确诊、预后监测及胚胎干细胞的分离纯化、鉴定等研究领域的重要应用价值;探讨了SSEA-1合成的关键酶——岩藻糖基转移酶基因表达与调控的研究进展。
