[Association of Crohn's disease with transcobalamin Ⅱ gene polymorphisms and serum homocysteine, folate and vitamin B12 levels in Chinese patients].

OBJECTIVE: To investigate the association of Crohn's disease (CD) with transcobalamin Ⅱ (TCN2) gene polymorphisms and serum homocysteine (Hcy), folate, and vitamin B12 levels in Chinese patients.

METHODS: In a total of 307 CD patients (CD group) and 574 healthy controls (control group) of Han ethnicity selected at 4 hospitals in Wenzhou between January 2007 and August 2015, TCN2 gene polymorphisms (rs1801198, C/G; rs9606756, A/G) in peripheral blood were determined using improved multiple ligase detection reaction (iMLDR). The Simplified Crohn's Disease Activity Index (CDAI) was applied to evaluate activity of CD. Eighty-eight CD patients and 138 age- and sex-matched controls were randomly selected from all the study subjects using computer-generated random numbers, in whom serum Hcy level was tested by enzymatic cycling assay, folate and vitamin B12 levels were examined by chemiluminescence immunoassay.

RESULTS: (1) The mutant allele (G) and genotype (CG+ GG) of rs1801198 were not significantly different between the CD group and the control group (both P>0.05), but more prevalent in patients with stricturing CD than in controls (65.75% vs 56.10%, 93.15% vs 82.40%, both P<0.05). The frequencies of mutant allele (G) and heterozygous genotype (AG) of rs9606756 were higher in CD patients than in controls (2.44% vs 1.05%, 4.89% vs 2.09%, both P<0.05), also higher in patients with stricturing CD or ileocolonic CD compared with controls (stricturing CD: 4.79% vs 1.05%, 9.59% vs 2.09%; ileocolonic CD: 3.18% vs 1.05%, 6.36% vs 2.09%; all P<0.05). The two polymorphic loci (rs1801198 and rs9606756) were shown to be in a weak linkage disequilibrium. The frequency of haplotype (GG) was higher in the CD patients than in the controls (2.23% vs 0.81%, P<0.05). (2) When compared with the controls, the serum Hcy level was higher in the CD patients (P=0.023), whereas the folate and vitamin B12 levels were decreased in the CD patients (both P<0.001). The prevalence of hyperhomocysteinemia (Hcy >15 μmol/L), folate deficiency (folate <4 μg/L) and vitamin B12 deficiency (<203 ng/L) were higher in the CD patients than in the controls (18.18% vs 4.35%, 27.27% vs 5.07%, 31.82% vs 5.07%, all P<0.01). Compared to the patients at remission stage (CDAI<5), the serum Hcy level was increased in those at active stage (CDAI≥5) (P=0.005), while the folate and vitamin B12 levels were decreased in the patients ate active stage (both P<0.05). (3) According to the results of multivariate linear regression analysis, average Hcy level in the CD patients was negatively associated with folate level (β=-0.494, P<0.001), while positively correlated with percentage of neutrophils (β=0.294, P=0.004). Unconditional Logistic regression showed that both folate deficiency and vitamin B12 deficiency were independent risk factors for CD (OR=5.415, OR=7.112, both P<0.001).

CONCLUSIONS: TCN2 rs1801198 mutation might be associated with increased risk of stricturing CD. TCN2 rs9606756 mutation might be a potential functional locus to affect CD susceptibility. Individuals carrying the haplotype (GG) formed by TCN2 (rs1801198 and rs9606756) seem to be at higher risk of developing CD. Hyperhomocysteinemia, folate deficiency, and vitamin B12 deficiency are prevalent in this cohort of CD patients of Han ethnicity from Zhejiang province. Both folate deficiency and vitamin B12 deficiency are independent risk factors for CD.