Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational Study
<p>Abstract</p> <p>Background</p> <p>Increased IL-18 serum levels have been associated with diabetes type 2, metabolic syndrome and the severity of atherosclerosis. The present study investigated the presence and influence of IL-18 genetic variants on gene- and protein...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-12-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | http://www.cardiab.com/content/10/1/110 |
| _version_ | 1819089178171801600 |
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| author | Opstad Trine B Pettersen Alf Å Arnesen Harald Seljeflot Ingebjørg |
| author_facet | Opstad Trine B Pettersen Alf Å Arnesen Harald Seljeflot Ingebjørg |
| author_sort | Opstad Trine B |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Increased IL-18 serum levels have been associated with diabetes type 2, metabolic syndrome and the severity of atherosclerosis. The present study investigated the presence and influence of IL-18 genetic variants on gene- and protein expression in stable coronary artery disease (CAD) patients.</p> <p>Methods</p> <p>The +183 A/G (rs 5744292), -137 G/C (rs 187238) and -607 C/A (rs 1946518) polymorphisms were determined in 1001 patients with angiographically verified stable CAD, and in 204 healthy controls. IL-18 gene-expression was measured in circulating leukocytes in 240 randomly selected patients. Circulating IL-18 and IL-18 binding protein levels were measured immunologically in all patients.</p> <p>Results</p> <p>The +183 G-allele associated significantly with lower serum levels of IL-18 (<it>p </it>= 0.002, adjusted for age, glucose, body mass index and gender) and a 1.13- fold higher IL-18 gene-expression (<it>p </it>= 0.010). No influence was observed for the -137 G/C and -607 C/A polymorphisms. The IL-18 binding protein levels were not influenced by IL-18 genotypes. IL-18 levels were significantly higher in men as compared to women, and in patients with diabetes type 2 and metabolic syndrome compared to those without (<it>p </it>≤ 0.001, all). The reduction in IL-18 levels according to the +183 G-allele was 3-4 fold more pronounced in diabetes and metabolic syndrome as compared to unaffected patients.</p> <p>Finally, the +183 AA genotype was more frequent in patients with hypertension (<it>p </it>= 0.042, adjusted for age, body mass index and gender).</p> <p>Conclusion</p> <p>The reduction in serum IL-18 levels across increasing numbers of +183G-alleles was especially apparent in patient with diabetes type 2 and metabolic syndrome, suggesting a beneficial GG genotype in relation to cardiovascular outcome in these patients.</p> <p>Clinical Trial Registration Number</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00222261">NCT00222261</a></p> |
| first_indexed | 2024-12-21T22:03:48Z |
| format | Article |
| id | doaj.art-80af7aca59734beea2b09886a49ed423 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-12-21T22:03:48Z |
| publishDate | 2011-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-80af7aca59734beea2b09886a49ed4232022-12-21T18:48:45ZengBMCCardiovascular Diabetology1475-28402011-12-0110111010.1186/1475-2840-10-110Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational StudyOpstad Trine BPettersen Alf ÅArnesen HaraldSeljeflot Ingebjørg<p>Abstract</p> <p>Background</p> <p>Increased IL-18 serum levels have been associated with diabetes type 2, metabolic syndrome and the severity of atherosclerosis. The present study investigated the presence and influence of IL-18 genetic variants on gene- and protein expression in stable coronary artery disease (CAD) patients.</p> <p>Methods</p> <p>The +183 A/G (rs 5744292), -137 G/C (rs 187238) and -607 C/A (rs 1946518) polymorphisms were determined in 1001 patients with angiographically verified stable CAD, and in 204 healthy controls. IL-18 gene-expression was measured in circulating leukocytes in 240 randomly selected patients. Circulating IL-18 and IL-18 binding protein levels were measured immunologically in all patients.</p> <p>Results</p> <p>The +183 G-allele associated significantly with lower serum levels of IL-18 (<it>p </it>= 0.002, adjusted for age, glucose, body mass index and gender) and a 1.13- fold higher IL-18 gene-expression (<it>p </it>= 0.010). No influence was observed for the -137 G/C and -607 C/A polymorphisms. The IL-18 binding protein levels were not influenced by IL-18 genotypes. IL-18 levels were significantly higher in men as compared to women, and in patients with diabetes type 2 and metabolic syndrome compared to those without (<it>p </it>≤ 0.001, all). The reduction in IL-18 levels according to the +183 G-allele was 3-4 fold more pronounced in diabetes and metabolic syndrome as compared to unaffected patients.</p> <p>Finally, the +183 AA genotype was more frequent in patients with hypertension (<it>p </it>= 0.042, adjusted for age, body mass index and gender).</p> <p>Conclusion</p> <p>The reduction in serum IL-18 levels across increasing numbers of +183G-alleles was especially apparent in patient with diabetes type 2 and metabolic syndrome, suggesting a beneficial GG genotype in relation to cardiovascular outcome in these patients.</p> <p>Clinical Trial Registration Number</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00222261">NCT00222261</a></p>http://www.cardiab.com/content/10/1/110Single nucleotide polymorphismsIL-18 mRNAdiabetes type 2metabolic syndromehypertension |
| spellingShingle | Opstad Trine B Pettersen Alf Å Arnesen Harald Seljeflot Ingebjørg Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational Study Cardiovascular Diabetology Single nucleotide polymorphisms IL-18 mRNA diabetes type 2 metabolic syndrome hypertension |
| title | Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational Study |
| title_full | Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational Study |
| title_fullStr | Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational Study |
| title_full_unstemmed | Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational Study |
| title_short | Circulating levels of IL-18 are significantly influenced by the IL-18 +183 A/G polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome: an Observational Study |
| title_sort | circulating levels of il 18 are significantly influenced by the il 18 183 a g polymorphism in coronary artery disease patients with diabetes type 2 and the metabolic syndrome an observational study |
| topic | Single nucleotide polymorphisms IL-18 mRNA diabetes type 2 metabolic syndrome hypertension |
| url | http://www.cardiab.com/content/10/1/110 |
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