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 19 November 2017

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MDR1 gene determines susceptibility to ulcerative colitis

Allelic variations of the MDR1 gene determine disease extent as well as susceptibility to ulcerative colitis in the Scottish population, find the most recent Gastroetnerology and present data strongly implicates the C3435T SNP.

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The MDR1 gene encodes P-glycoprotein 170, an efflux transporter that is highly expressed in intestinal epithelial cells.

The MDR1 exonic single nucleotide polymorphisms (SNPs) C3435T and G2677T have been shown to correlate with activity/expression of P-glycoprotein 170.

Dr Nimmo and colleagues from Edinburgh, Scotland undertook a case-control analysis of MDR1 C3435T and G2677T SNPs in a large well-characterized Scottish white cohort.

The research team enrolled 335 patients with ulcerative colitis [UC], 268 with Crohn’s disease [CD], and 370 healthy controls).

The researchers conducted 2-locus haplotype and detailed univariate and multivariate genotypic-phenotypic analyses.

The research team found that the MDR1 3435 TT genotype (34.6% vs 26.5%) and T-allelic frequencies (58.2% vs 52.8%) were significantly higher in patients with ulcerative colitis compared with controls.

The researchers found no association with Crohn's disease.

G2677T SNP was not associated with ulcerative colitis or Crohn's disease
Gastroenterology

The research team found that the association was strongest with extensive ulcerative colitis and they were able to confirm this on multivariate analysis.

The G2677T SNP was not associated with ulcerative colitis or Crohn's disease.

These 2 SNPs lie in linkage disequilibrium in our population.

The researchers found that 2-locus haplotypes showed both positive and negative associations with ulcerative colitis.

Homozygotes for the haplotype 3435T/G2677 were significantly increased in ulcerative colitis.

Dr Nimmo concluded, "Allelic variations of the MDR1 gene determine disease extent as well as susceptibility to ulcerative colitis in the Scottish population."

"The present data strongly implicate the C3435T SNP, although the 2-locus haplotype data underline the need for further detailed haplotypic studies."

Gastroenterology; 2005: 128 (2): 288
03 February 2005

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