Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels
The genomic region ~500 kb upstream of IRS1 has been implicated in insulin resistance, type 2 diabetes, adverse lipid profile, and cardiovascular risk. To gain further insight into this chromosomal region, we typed four SNPs in a cross-sectional cohort and subjects with type 2 diabetes recruited fro...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/405371 |
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| author | Selma M. Soyal Thomas Felder Simon Auer Hannes Oberkofler Bernhard Iglseder Bernhard Paulweber Silvia Dossena Charity Nofziger Markus Paulmichl Harald Esterbauer Franz Krempler Wolfgang Patsch |
| author_facet | Selma M. Soyal Thomas Felder Simon Auer Hannes Oberkofler Bernhard Iglseder Bernhard Paulweber Silvia Dossena Charity Nofziger Markus Paulmichl Harald Esterbauer Franz Krempler Wolfgang Patsch |
| author_sort | Selma M. Soyal |
| collection | DOAJ |
| description | The genomic region ~500 kb upstream of IRS1 has been implicated in insulin resistance, type 2 diabetes, adverse lipid profile, and cardiovascular risk. To gain further insight into this chromosomal region, we typed four SNPs in a cross-sectional cohort and subjects with type 2 diabetes recruited from the same geographic region. From 16 possible haplotypes, 6 haplotypes with frequencies >0.01 were observed. We identified one haplotype that was protective against insulin resistance (determined by HOMA-IR and fasting plasma insulin levels), type 2 diabetes, an adverse lipid profile, increased C-reactive protein, and asymptomatic atherosclerotic disease (assessed by intima media thickness of the common carotid arteries). BMI and total adipose tissue mass as well as visceral and subcutaneous adipose tissue mass did not differ between the reference and protective haplotypes. In 92 subjects, we observed an association of the protective haplotype with higher skeletal muscle mRNA levels of LOC646736, which is located in the same haplotype block as the informative SNPs and is mainly expressed in skeletal muscle, but only at very low levels in liver or adipose tissues. These data suggest a role for LOC646736 in human insulin resistance and warrant further studies on the functional effects of this locus. |
| format | Article |
| id | doaj-art-0b571fa4bbbb4d6e99dcfec93d6abc8e |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-0b571fa4bbbb4d6e99dcfec93d6abc8e2025-08-20T03:54:28ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/405371405371Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA LevelsSelma M. Soyal0Thomas Felder1Simon Auer2Hannes Oberkofler3Bernhard Iglseder4Bernhard Paulweber5Silvia Dossena6Charity Nofziger7Markus Paulmichl8Harald Esterbauer9Franz Krempler10Wolfgang Patsch11Institute of Pharmacology and Toxicology, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Geriatric Medicine, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Internal Medicine I, Paracelsus Medical University, 5020 Salzburg, AustriaInstitute of Pharmacology and Toxicology, Paracelsus Medical University, 5020 Salzburg, AustriaInstitute of Pharmacology and Toxicology, Paracelsus Medical University, 5020 Salzburg, AustriaInstitute of Pharmacology and Toxicology, Paracelsus Medical University, 5020 Salzburg, AustriaDepartment of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Internal Medicine, Krankenhaus Hallein, 5400 Hallein, AustriaInstitute of Pharmacology and Toxicology, Paracelsus Medical University, 5020 Salzburg, AustriaThe genomic region ~500 kb upstream of IRS1 has been implicated in insulin resistance, type 2 diabetes, adverse lipid profile, and cardiovascular risk. To gain further insight into this chromosomal region, we typed four SNPs in a cross-sectional cohort and subjects with type 2 diabetes recruited from the same geographic region. From 16 possible haplotypes, 6 haplotypes with frequencies >0.01 were observed. We identified one haplotype that was protective against insulin resistance (determined by HOMA-IR and fasting plasma insulin levels), type 2 diabetes, an adverse lipid profile, increased C-reactive protein, and asymptomatic atherosclerotic disease (assessed by intima media thickness of the common carotid arteries). BMI and total adipose tissue mass as well as visceral and subcutaneous adipose tissue mass did not differ between the reference and protective haplotypes. In 92 subjects, we observed an association of the protective haplotype with higher skeletal muscle mRNA levels of LOC646736, which is located in the same haplotype block as the informative SNPs and is mainly expressed in skeletal muscle, but only at very low levels in liver or adipose tissues. These data suggest a role for LOC646736 in human insulin resistance and warrant further studies on the functional effects of this locus.http://dx.doi.org/10.1155/2015/405371 |
| spellingShingle | Selma M. Soyal Thomas Felder Simon Auer Hannes Oberkofler Bernhard Iglseder Bernhard Paulweber Silvia Dossena Charity Nofziger Markus Paulmichl Harald Esterbauer Franz Krempler Wolfgang Patsch Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels Journal of Diabetes Research |
| title | Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels |
| title_full | Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels |
| title_fullStr | Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels |
| title_full_unstemmed | Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels |
| title_short | Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels |
| title_sort | associations of haplotypes upstream of irs1 with insulin resistance type 2 diabetes dyslipidemia preclinical atherosclerosis and skeletal muscle loc646736 mrna levels |
| url | http://dx.doi.org/10.1155/2015/405371 |
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