Intest Res.  2015 Jul;13(3):242-249. 10.5217/ir.2015.13.3.242.

Polymorphisms in PRKCDBP, a Transcriptional Target of TNF-alpha, Are Associated With Inflammatory Bowel Disease in Korean

Affiliations
  • 1Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea. gidrlee@paran.com
  • 2School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.

Abstract

BACKGROUND/AIMS
Emerging data indicate that polymorphic sequence variations in the tumor necrosis factor alpha (TNF-alpha) gene may affect its production, and be associated with the risk of inflammatory bowel disease (IBD). PRKCDBP is a putative tumor suppressor gene and a transcriptional target of TNF-alpha. The aim of this case-control study is to explore the possible association of single nucleotide polymorphisms (SNPs) in PRKCDBP with the development of IBD in Koreans.
METHODS
Genotyping analysis of four SNPs of PRKCDBP [rs35301211 (G210A), rs11544766 (G237C), rs12294600 (C797T), and rs1051992 (T507C)] was performed on 170 ulcerative colitis (UC),131 Crohn's disease (CD) patients, and 100 unrelated healthy controls using polymerase chain reaction and restriction fragment length polymorphism.
RESULTS
Heterozygous configuration of three SNPs (G210A, G237C, and C797T) was very rare in both patients and healthy controls. However, allele frequencies of the T507C SNP showed a significant difference between UC patients and controls (P=0.037). The CC genotype of the T507C SNP was identified in 46.6% (61 of 131) of CD and 49.4% (84 of 170) of UC patients, but only in 33.0% (33 of 100) of healthy controls. Furthermore, CC homozygosity was more prevalent than TC heterozygosity in both CD and UC patients versus controls (P=0.016; gender-adjusted odds ratio [aOR], 2.16; 95% confidence interval [CI], 1.16-4.04 and P=0.009; aOR, 2.09; 95% CI, 1.193.64; respectively)
CONCLUSIONS
Our results suggest that the T507C SNP in PRKCDBP, a TNF-alpha-inducible gene, might be associated with susceptibility to IBD (particularly UC) development in Koreans.

Keyword

PRKCDBP; Polymorphisms, single nucleotide; Crohn disease; Colitis, ulcerative

MeSH Terms

Case-Control Studies
Colitis, Ulcerative
Crohn Disease
Gene Frequency
Genes, Tumor Suppressor
Genotype
Humans
Inflammatory Bowel Diseases*
Odds Ratio
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide
Tumor Necrosis Factor-alpha*
Tumor Necrosis Factor-alpha

Figure

  • Fig. 1 Representative genotyping of single nucleotide polymorphisms (SNPs) by PCR-RFLP. (A) Genotype analysis of the G201A SNP. The 208-bp fragment is the undigested PCR product of the A allele. Two fragments of 184 and 24 bp lengths result from SphI digestion of the G allele. Only the 184-bp fragment was detectable on a 2% agarose gel. (B) Genotype analysis of the G237C SNP. The 339-bp fragment is the undigested PCR product of the C allele. Two fragments of 199 and 140 bp lengths result from DdeI digestion of the G allele. (C) Genotype analysis of the C797T SNP. The 231-bp fragment is the undigested PCR product of the T allele. Two fragments of 209 and 22 bp lengths result from BtsI digestion of the C allele. Only the 209-bp fragment was detected.

  • Fig. 2 The T507C single nucleotide polymorphisms (SNP). (A) The genomic sequence region flanking the T507C single nucleotide polymorphism (SNP) site. It was amplified by PCR using primers SRBC507-1 and SRBC507-2 (underlined). The SNP site is denoted by bold text and a box. (B) Representative genotyping of the PRKCDBP rs1051992 (T507C) SNP. The 199 bp fragment is the undigested product of the C allele. Fragments of 167 and 32 bp lengths result from PvuII digestion of the T allele. Only the 167 bp fragment of the digested PCR products was detectable on a 2% agarose gel.


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