Walters, J.R.F.; Van Heel, D.A.; Khanji, M.; Rhodes-Kendler, O.; Khair, U.; Barley, N.F.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA7
Academic Journal
The absorption of dietary calcium by the intestine varies between individuals and those with Iow absorption are at greater risk of osteoporotic fractures. Only part of the variation is dependent on circulating vitamin D metabolites and the differences in intestinal expression of genes involved in calcium transport remain unexplained. The aim of this study was to investigate whether polymorphisms in two key genes could be implicated in the observed differences. The expression of the epithelial apical membrane calcium transporter, ECAC2/CAT1 (TRPV6 gene) differs tenfold between individuals. Approximately 1.5 kb of the 5' flanking region of this gene was sequenced in DNA from 15 subjects including 13 with known levels of duodenal ECAC2/CAT1 RNA expression' Only one DNA contained a single nucleotide polymorphism SNP and this was from a subject with expression in the mid-range. A novel polymorphism in the vitamin D receptor (VDR) gene has recently been associated with differences in bone density in a Japanese population. This SNP (G or A) is in a caudal-related homeobox (CDX2) binding element and has been shown to affect transcription of the VDR gene. It was hypothesised that differences in expression of the VDR in the intestine could then affect the expression of vitamin D dependent genes involved in calcium absorption. In 82 British patients the allelic frequencies of this SNP were G:A = 0.76:0.24, different to those found in Japan. There were relatively few AA homozygotes and no sign f cant differences could be demonstrated in bone mineral density. The SNP genotypes were not associated with differences in mean levels of expression of duodenal calcium transport genes (ECAC2/ CAT1, calbindin-D9k, or PMCA1), although there was evidence of significantly different responsiveness to 1,25-(OH)[sub 2]D[sub 3]. In summary, no significant SNP has been found in the promoter of the gene for ECAC2/CAT1, but the effect of the CDX2 binding element SNP in the VDR gene merits...


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