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Diabetic retinopathy, PAI-1 4G/5G and -844G/A polymorphisms, and changes in circulating PAI-1 levels in Tunisian type 2 diabetes patients.
Diabetes Metab. 2009 Jun; 35(3):214-9.DM

Abstract

AIM

The association of altered plasminogen activator inhibitor (PAI)-1 levels and PAI-1 polymorphisms (4G/5G and -844G/A) with diabetic retinopathy (DR) was investigated in 856 type 2 diabetes (T2D) patients, of whom 383 presented with (DR group), and 473 presented without (DWR group), retinopathy.

METHODS

PAI-1 4G/5G and -844G/A genotyping were done by PCR-RFLP, and PAI-1 levels were measured by ELISA testing.

RESULTS

The genotype distribution of 4G/5G and -844G/A polymorphisms did not deviate from the Hardy-Weinberg equilibrium model among healthy subjects. Higher frequencies of the 4G/4G genotype, and lower frequencies of the -844A allele, -844G/A and -844A/A genotypes, were seen in DR patients, conferring disease susceptibility and protection, respectively. While PAI-1 levels were significantly elevated in the 4G/4G compared with other PAI-1 genotypes, significant differences in PAI-1 levels between DR and DWR patients were seen in the 4G/-844A, 4G/-844G and 5G/-844A haplotype carriers among DR patients. However, comparable distributions of 4G/5G and -844G/A alleles, genotypes and haplotypes, and similar PAI-1 levels, were seen in the proliferative retinopathy (PR) and non-proliferative retinopathy (NPR) patients, indicating that neither PAI-1 variants nor changes in PAI-1 levels were linked to DR severity. Multivariate analyses identified 4G/-844A and 4G/-844G haplotypes as negatively and positively associated, respectively, with DR, but not with DR severity (PR vs NPR) after adjusting for a number of covariates.

CONCLUSION

The present study identifies changes in PAI-1 levels and genetic variations at the PAI-1 locus as risk factors for DR, but not DR severity, that may serve as useful markers of increased DR susceptibility.

Authors+Show Affiliations

Faculty of Pharmacy of Monastir, University of Monastir, Monastir, Tunisia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19419896

Citation

Ezzidi, I, et al. "Diabetic Retinopathy, PAI-1 4G/5G and -844G/A Polymorphisms, and Changes in Circulating PAI-1 Levels in Tunisian Type 2 Diabetes Patients." Diabetes & Metabolism, vol. 35, no. 3, 2009, pp. 214-9.
Ezzidi I, Mtiraoui N, Chaieb M, et al. Diabetic retinopathy, PAI-1 4G/5G and -844G/A polymorphisms, and changes in circulating PAI-1 levels in Tunisian type 2 diabetes patients. Diabetes Metab. 2009;35(3):214-9.
Ezzidi, I., Mtiraoui, N., Chaieb, M., Kacem, M., Mahjoub, T., & Almawi, W. Y. (2009). Diabetic retinopathy, PAI-1 4G/5G and -844G/A polymorphisms, and changes in circulating PAI-1 levels in Tunisian type 2 diabetes patients. Diabetes & Metabolism, 35(3), 214-9. https://doi.org/10.1016/j.diabet.2008.12.002
Ezzidi I, et al. Diabetic Retinopathy, PAI-1 4G/5G and -844G/A Polymorphisms, and Changes in Circulating PAI-1 Levels in Tunisian Type 2 Diabetes Patients. Diabetes Metab. 2009;35(3):214-9. PubMed PMID: 19419896.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diabetic retinopathy, PAI-1 4G/5G and -844G/A polymorphisms, and changes in circulating PAI-1 levels in Tunisian type 2 diabetes patients. AU - Ezzidi,I, AU - Mtiraoui,N, AU - Chaieb,M, AU - Kacem,M, AU - Mahjoub,T, AU - Almawi,W Y, Y1 - 2009/05/05/ PY - 2008/04/16/received PY - 2008/11/29/revised PY - 2008/12/01/accepted PY - 2009/5/8/entrez PY - 2009/5/8/pubmed PY - 2009/9/18/medline SP - 214 EP - 9 JF - Diabetes & metabolism JO - Diabetes Metab VL - 35 IS - 3 N2 - AIM: The association of altered plasminogen activator inhibitor (PAI)-1 levels and PAI-1 polymorphisms (4G/5G and -844G/A) with diabetic retinopathy (DR) was investigated in 856 type 2 diabetes (T2D) patients, of whom 383 presented with (DR group), and 473 presented without (DWR group), retinopathy. METHODS: PAI-1 4G/5G and -844G/A genotyping were done by PCR-RFLP, and PAI-1 levels were measured by ELISA testing. RESULTS: The genotype distribution of 4G/5G and -844G/A polymorphisms did not deviate from the Hardy-Weinberg equilibrium model among healthy subjects. Higher frequencies of the 4G/4G genotype, and lower frequencies of the -844A allele, -844G/A and -844A/A genotypes, were seen in DR patients, conferring disease susceptibility and protection, respectively. While PAI-1 levels were significantly elevated in the 4G/4G compared with other PAI-1 genotypes, significant differences in PAI-1 levels between DR and DWR patients were seen in the 4G/-844A, 4G/-844G and 5G/-844A haplotype carriers among DR patients. However, comparable distributions of 4G/5G and -844G/A alleles, genotypes and haplotypes, and similar PAI-1 levels, were seen in the proliferative retinopathy (PR) and non-proliferative retinopathy (NPR) patients, indicating that neither PAI-1 variants nor changes in PAI-1 levels were linked to DR severity. Multivariate analyses identified 4G/-844A and 4G/-844G haplotypes as negatively and positively associated, respectively, with DR, but not with DR severity (PR vs NPR) after adjusting for a number of covariates. CONCLUSION: The present study identifies changes in PAI-1 levels and genetic variations at the PAI-1 locus as risk factors for DR, but not DR severity, that may serve as useful markers of increased DR susceptibility. SN - 1262-3636 UR - https://www.unboundmedicine.com/medline/citation/19419896/Diabetic_retinopathy_PAI_1_4G/5G_and__844G/A_polymorphisms_and_changes_in_circulating_PAI_1_levels_in_Tunisian_type_2_diabetes_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1262-3636(09)00048-2 DB - PRIME DP - Unbound Medicine ER -