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PAI-1 Gene 4G/5G polymorphism and risk of type 2 diabetes in a population-based sample.
Obesity (Silver Spring). 2006 May; 14(5):753-8.O

Abstract

Elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) increase risk for type 2 diabetes. The PAI-1 4G/5G polymorphism is a major genetic determinant of plasma PAI-1 levels, with 4G/4G homozygotes having elevated PAI-1 levels relative to 5G allele carriers. These observations suggest the hypothesis that the PAI-1 4G/5G polymorphism could be a genetic risk factor for diabetes. We tested this hypothesis among 2169 participants of the Framingham Offspring Study followed for seven examinations over 26 years for 216 cases of type 2 diabetes. PAI-1 4G/4G homozygotes (genotype frequency, 27.4%) were not at significantly (p > 0.05) increased risk of incident diabetes compared with 5G allele carriers and did not have elevated levels of diabetes-related quantitative traits including BMI, fasting plasma glucose, or fasting insulin. In proportional hazards regression models accounting for correlation among siblings, with the 5G/5G genotype as the referent, the hazard ratio for incident diabetes for 4G/5G carriers was 0.93 (95% confidence interval, 0.68 to 1.28) and for 4G/4G carriers was 1.20 (95% confidence interval, 0.83 to 1.92). Results were not altered by further adjustment for sex or levels of BMI, triglycerides, or PAI-1. We conclude that the PAI-1 4G/5G polymorphism is not an important genetic risk factor for type 2 diabetes in this community-based sample. Elevated PAI-1 levels may be associated with an increased risk for diabetes as a marker for underlying endothelial dysfunction rather than by a direct effect of genetically mediated elevated levels.

Authors+Show Affiliations

General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. jmeigs@partners.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16855181

Citation

Meigs, James B., et al. "PAI-1 Gene 4G/5G Polymorphism and Risk of Type 2 Diabetes in a Population-based Sample." Obesity (Silver Spring, Md.), vol. 14, no. 5, 2006, pp. 753-8.
Meigs JB, Dupuis J, Liu C, et al. PAI-1 Gene 4G/5G polymorphism and risk of type 2 diabetes in a population-based sample. Obesity (Silver Spring). 2006;14(5):753-8.
Meigs, J. B., Dupuis, J., Liu, C., O'Donnell, C. J., Fox, C. S., Kathiresan, S., Gabriel, S. B., Larson, M. G., Yang, Q., Herbert, A. G., Wilson, P. W., Feng, D., Tofler, G. H., & Cupples, L. A. (2006). PAI-1 Gene 4G/5G polymorphism and risk of type 2 diabetes in a population-based sample. Obesity (Silver Spring, Md.), 14(5), 753-8.
Meigs JB, et al. PAI-1 Gene 4G/5G Polymorphism and Risk of Type 2 Diabetes in a Population-based Sample. Obesity (Silver Spring). 2006;14(5):753-8. PubMed PMID: 16855181.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PAI-1 Gene 4G/5G polymorphism and risk of type 2 diabetes in a population-based sample. AU - Meigs,James B, AU - Dupuis,Josée, AU - Liu,Chunyu, AU - O'Donnell,Christopher J, AU - Fox,Caroline S, AU - Kathiresan,Sekar, AU - Gabriel,Stacey B, AU - Larson,Martin G, AU - Yang,Qiong, AU - Herbert,Alan G, AU - Wilson,Peter W F, AU - Feng,Dali, AU - Tofler,Geoffrey H, AU - Cupples,L Adrienne, PY - 2006/7/21/pubmed PY - 2006/12/9/medline PY - 2006/7/21/entrez SP - 753 EP - 8 JF - Obesity (Silver Spring, Md.) JO - Obesity (Silver Spring) VL - 14 IS - 5 N2 - Elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) increase risk for type 2 diabetes. The PAI-1 4G/5G polymorphism is a major genetic determinant of plasma PAI-1 levels, with 4G/4G homozygotes having elevated PAI-1 levels relative to 5G allele carriers. These observations suggest the hypothesis that the PAI-1 4G/5G polymorphism could be a genetic risk factor for diabetes. We tested this hypothesis among 2169 participants of the Framingham Offspring Study followed for seven examinations over 26 years for 216 cases of type 2 diabetes. PAI-1 4G/4G homozygotes (genotype frequency, 27.4%) were not at significantly (p > 0.05) increased risk of incident diabetes compared with 5G allele carriers and did not have elevated levels of diabetes-related quantitative traits including BMI, fasting plasma glucose, or fasting insulin. In proportional hazards regression models accounting for correlation among siblings, with the 5G/5G genotype as the referent, the hazard ratio for incident diabetes for 4G/5G carriers was 0.93 (95% confidence interval, 0.68 to 1.28) and for 4G/4G carriers was 1.20 (95% confidence interval, 0.83 to 1.92). Results were not altered by further adjustment for sex or levels of BMI, triglycerides, or PAI-1. We conclude that the PAI-1 4G/5G polymorphism is not an important genetic risk factor for type 2 diabetes in this community-based sample. Elevated PAI-1 levels may be associated with an increased risk for diabetes as a marker for underlying endothelial dysfunction rather than by a direct effect of genetically mediated elevated levels. SN - 1930-7381 UR - https://www.unboundmedicine.com/medline/citation/16855181/PAI_1_Gene_4G/5G_polymorphism_and_risk_of_type_2_diabetes_in_a_population_based_sample_ L2 - https://doi.org/10.1038/oby.2006.85 DB - PRIME DP - Unbound Medicine ER -