Association of fucosyltransferase 2 gene variants with ulcerative colitis in Han and Uyghur patients in China

Abstract

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 populations (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 between patients 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, su...

Association of Ulcerative Colitis with FUT2 and FUT3 Polymorphisms in Patients from Southeast China

“…However, in a Finnish population the wild GG genotype of FUT2 (rs601338) was associated with enhanced risk of UC [ 24 ]. And in a Chinese Han population mutations in FUT2 (rs281377 and rs601338) predisposed patients to UC, while FUT2 (rs1047781 and rs601338) polymorphisms were associated with UC in Uyghur population from northwest China [ 37 ]. In this study we found no association between FUT2 polymorphisms and UC.…”

Associations of FUT2 and FUT3 gene polymorphisms with Crohn's disease in Chinese patients

“…Furthermore, we compared the current study with a previous one, which was also carried out on associations of UC with FUT2 polymorphisms in Chinese patients. 29 Consequently, the allele and genotypic distributions of FUT2 gene in the controls were presented to be inconsistent in the two studies. We conjectured that it might be mainly due to the discrepancy of the study sample sizes.…”

“…28 In Chinese population, moreover, (rs281377) and (rs601338) of FUT2 were implicated in the susceptibility to UC. 29 As far as we know, few studies to date have been simultaneously on the associations of CD with FUT2 and FUT3 polymorphisms. Based on the above findings, we conjectured that secretor status and/or Lewis status determined by polymorphisms of FUT2 and FUT3 might alter the predisposition of CD possibly by affecting intestinal microbiota and innate immune responses.…”

Association of Fucosyltransferase 2 Gene Polymorphisms with Inflammatory Bowel Disease in Patients from Southeast China

“…This is inconsistent with the results from another study, in which the FUT2 G428A mutant genotype (AA+GA) in the Finland population increased the susceptibility to UC [ 11 ]. In addition, studies in China showed that the FUT2 gene A385T polymorphism is not associated with the susceptibility to UC in the Chinese Han nationality, but the functional mutations of C357T and G428A are in accordance with the susceptibility to IBD of the Han nationality [ 15 ]. Thus, it can be inferred that the effect of FUT2 gene polymorphism on susceptibility to IBD may be closely related to the ethnic differences.…”

“…McGovern et al reported in Caucasian population that FUT2 nonsecretor status is associated with Crohn's disease [ 14 ]. The role of FUT2 gene in UC has also been investigated, but the results seem to lack consistency [ 11 , 15 ]. Therefore, this study aimed to explore the relationship between FUT2 gene polymorphism and IBD susceptibility in the Chinese population, which might provide a genetic basis for the mechanism of IBD and find potential new therapeutic targets.…”