Biomedical subjects

Jutta Palmen

Publications and source records attributed to Jutta Palmen.

4 recordsLinked to original sources

PubMed2005

The microsatellite polymorphism of heme oxygenase-1 is associated with baseline plasma IL-6 level but not with restenosis after coronary in-stenting.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Adult↗

PubMed2005

Determination of the functionality of common APOA5 polymorphisms.

Common variants of APOA5 have consistently shown association with differences in plasma triglyceride (TG) levels. These single nucleotide polymorphisms (SNPs) fall into three common haplotypes: APOA5*1, with common alleles at all sites; APOA5*2, with rare alleles of -1131T--> C, -3A--> G, 751G--> T, and 1891T--> C; and APOA5*3, distinguished by the c56C--> G (S19W). Molecular modeling of the apoAV signal peptide (SP) showed an increased angle of insertion (65 degrees ) at the lipid/water interface of Trp-19 SP compared with Ser-19 SP (40 degrees ), predicting reduced translocation. This was confirmed by 50% reduction of Trp-19-encoded SP.secretory alkaline phosphatase (SEAP) fusion protein secreted into the medium from HepG2 cells compared with the Ser-19.SEAP fusion protein (p < 0.002). Considering APOA5*2 SNPs, there was no significant difference in the relative luciferase expression in Huh7 cells transiently transfected with a -1131T construct compared with the -1131C (fragments -1177 to -516 or -1177 to -3). Similarly, for the -3A--> G in the Kozak sequence, in vitro transcription/translation assays and primer extension inhibition assays showed no alternate AUG initiation codon usage, demonstrating that -3A--> G did not influence translation efficiency. Although 1891T--> C in the 3'-untranslated region disrupts a putative Oct-1 transcription factor binding site, when inserted 3' of the luciferase gene the T--> C change demonstrated no significant difference in luciferase expression. Thus, association of APOA5*2 SNPs with TG levels is not due to the individual effects of any of these SNPs, although cooperativity between the SNPs cannot be excluded. Alternatively, the effect on TG levels may reflect the strong linkage disequilibrium with the functional APOC3 SNPs.

3' Untranslated Regions↗

PubMed2005

Investigation into the role of the hormone sensitive lipase -60C>G promoter variant in morbid obesity.

BACKGROUND: Hormone sensitive lipase (HSL) plays a central role in free fatty acid homeostasis in adipose tissue and in pancreatic beta-cells, where it contributes to the control of insulin secretion by generating long-chain fatty acids. AIM: We examined the frequency and association of the functional HSL promoter variant, -60C>G, in a German cohort of morbidly obese women (N=239) and men (N=55) and compared the frequency to a cohort of 199 blood donors, recruited from the same region. RESULTS: The rare allele frequency of -60C>G, in the obese individuals was significantly lower 0.031 (95% CI 0.02, 0.04), than that in the blood donors 0.061 (95% CI 0.04, 0.08) p=0.05. The association of the HSL -60C>G with lipid and glucose parameters was examined in the obese women (there were too few men for comparative analysis). In the obese women, those heterozygous for the -60G had significantly higher glucose levels compared to CC women, 142.71 (+/-16.23) mg/dl vs. 110.34 (+/-1.79) mg/dl, respectively (p=0.0001). There was no statistically significant difference in other parameters. CONCLUSION: This study confirms a role for HSL in glucose homeostasis and the reduced frequency of the low expressing -60G promoter variant in obese individuals, together with existing published data, suggests that this allele might be protective against obesity.

Adult↗

PubMed2004

Variation in USF1 shows haplotype effects, gene : gene and gene : environment associations with glucose and lipid parameters in the European Atherosclerosis Research Study II.

Upstream stimulatory factor 1 (USF 1), is a transcription factor controlling expression of several genes involved in lipid and glucose homeostasis and co-localizes with familial combined hyperlipidemia (FCHL) and type 2 diabetes on chromosome 1q22-23. We sequenced USF1 in 24 UK FCHL probands, but found no rare or common cSNPs. Three common intronic single nucleotide ploymorphisms (SNP), 306A>G, 475C>T and 1748C>T, were identified and their association was examined with fasting and postprandial lipids and after an oral glucose tolerance test (OGTT) in the European Atherosclerosis Research Study II offspring study. There were no significant differences in allelic frequencies of the SNPs between cases and controls. Individually none of the SNPs showed significant associations with any parameter. In haplotype analysis, compared with other haplotypes, 475C/1748T showed significantly higher and 475T/1748T showed lower peak glucose (P=0.004 and 0.07, respectively) during the OGTT. There was significant case-control heterogeneity in the interaction of genotype with body mass index, on fasting low density lipoprotein with 306A>G and 1748C>T, and on borderline significance with fasting glucose with 475C>T (P=0.002, 0.0007 and 0.015, respectively). Furthermore, 475C>T showed interaction with both HSL-60C>G (case-control heterogeneity P=0.0002) on AUC TG and APOC3 -482C>T on plasma apoE levels (P=0.0012). Thus, in these healthy young men, variation in USF1 was the influencing feature of both glucose and lipid homeostasis showing case-control heterogeneity.

Adolescent↗