Genetic susceptibility to ulcerative colitis in the Chinese Han ethnic population: association with TNF polymorphisms.
BACKGROUND
Tumor necrosis factor alpha (TNFalpha) is an important proinflammatory cytokine that has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Recent studies have evaluated the role of TNF promoter polymorphisms in IBD, whereas the data are inconsistent. Trans-racial mapping in an ethnically distinct but homogenous population may help clarify these associations. We investigate the association between TNF promoter polymorphisms and susceptibility to ulcerative colitis (UC) in the Chinese Han ethnic population.


METHODS
We studied 110 unrelated UC patients and 292 healthy controls from Zhejiang Province, China. Genotyping for 6 common TNF promoter polymorphisms (TNF -1031T/C, -863C/A, -857C/T, -380G/A, -308G/A, -238G/A) was carried out by polymerase chain reaction sequence-specific primers (PCR-SSP).


RESULTS
TNF -308A was associated with disease (allele frequency patients 14.6% vs controls 8.9%, P = 0.02). TNF -857T was increased in patients but without statistical significance (allele frequency 17.3% vs 12.2%, P = 0.06). Haplotype analysis revealed 6 haplotypes including two (H5 and H3), which contained TNF -308A. H5 was associated with disease (haplotype frequency patients -12.3% vs controls 7.5%, P = 0.03). Of note the rare haplotype H3 has not previously been identified in Caucasian populations. Homozygosity for the haplotype H4 comprising the common alleles at each TNF promoter single-nucleotide polymorphism (SNP) was negatively associated with disease (patients vs controls 24.5% vs 34.9%, P < 0.05).


CONCLUSIONS
We report the association with TNF -308A polymorphisms in Chinese patients with ulcerative colitis. The functional study in Chinese Han ethnic population is now required.
Cao
Qian
Q
Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
Zhu
Qin
Q
Wu
Min-liang
ML
Hu
Wei-ling
WL
Gao
Min
M
Si
Jian-min
JM
D002681:China / Q000208:ethnology; D003093:Colitis, Ulcerative / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha