ABSTRACT
To determine the sequence variant of TLL1 gene [rs1503298, T > C] in three British cohorts [PREDICT, UDACS and ED] of patients with type-2 Diabetes mellitus [T2DM] in order to assess its association with coronary heart disease [CHD]. Analytical study. UCL, London, UK. Participants were genotyped in 2011-2012 for TLL1 SNP. Samples and related information were previously collected in 2001-2003 for PREDICT, and in 2001-2002 for UDACS and ED groups. Patients included in PREDICT [n=600], UDACS [n=1020] and ED [n=1240] had Diabetes. TLL1 SNP [rs1503298, T > C] was genotyped using TaqMan technology. Allele frequencies were compared using c2 test, and tested for Hardy-Weinberg equilibrium. The risk of disease was assessed from Odds ratios [OR] with 95% Confidence Intervals [95% CI]. Moreover, for the PREDICT cohort, the SNP association was tested with Coronary Artery Calcification [CAC] scores. No significant association was found for this SNP with CHD or CAC scores in these cohorts. This SNP could not be confirmed as a risk factor for CHD in T2DM patients. However, the low power of thesmall sample size available is a limitation to the modest effect on risk. Further studies in larger samples would be useful
ABSTRACT
<p><b>BACKGROUND</b>Vascular smooth muscle cells (VSMCs) can express heme-oxygenase (HO), a rate-limiting enzyme in the degradation of heme to bilirubin, ferritin and carbon monoxide (CO). VSMC-derived CO can suppress VSMC proliferation and may serve as an antiproliferation factor. The promoter region of HO-1 shows a polymorphism with different (GT) n repeats that has been reported to differently induce gene expression. The objective of this study was to examine the effect of this variation on the occurrence of restenosis after in-stent treatment in patients with coronary artery disease.</p><p><b>METHODS</b>Candidates who underwent coronary stent implantation were genotyped for the HO-1 promoter polymorphism using polymerase chain reaction (PCR) and automated DNA capillary sequencer. Serum levels of IL-6 and C-reactive protein (CRP) were obtained at baseline, 24 hours and 48 hours after stenting. The primary end point for the study was angiographic evidence of in-stent restenosis at 6 months. All parameters for evaluation of restenosis were analysed by quantitative computer-assisted angiographic analysis (QCA).</p><p><b>RESULTS</b>One hundred and eighty-seven patients who underwent coronary stent implantation were studied of whom 27.8% showed > or = 50% restenosis after 6 months. The distribution of (GT) n repeats of all patients in the promoter region of HO-1 genotype ranged from 22 to 42, with (GT) 25 and (GT) 32 being the two most common alleles. The allelic repeats were divided into the short class (S) with 29 (GT) n, the middle class (M) with 30-37 (GT) n and the long class (L) with 38 (GT) n. There was no significant difference in the restenosis between the genotype groups or between post operation levels of inflammation markers, but carriers of the S allele (n = 120) had 33.3% lower baseline IL-6 compared with non-S carriers (n = 67, P = 0.0008).</p><p><b>CONCLUSIONS</b>Although no association was observed between the HO-1 promoter polymorphism and coronary in-stent restenosis following the stent procedure, the association with plasma IL-6 levels suggests that HO-1 S allele might protect from the atherosclerotic inflammatory process.</p>