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Diabetic retinopathy, promoter (4G/5G) polymorphism of PAI-1 gene, and PAI-1 activity in Pima Indians with type 2 diabetes.
Diabetes Care 1997; 20(8):1304-9DC

Abstract

OBJECTIVE

To examine the relationship between plasma plasminogen activator inhibitor 1 (PAI-1) activity and PAI-1 gene (4G/5G) polymorphism and diabetic retinopathy in Pima Indians with type 2 diabetes.

RESEARCH DESIGN AND METHODS

We studied 171 Pima Indians with type 2 diabetes between the ages of 30-70 years in a population-based epidemiological survey. Plasma PAI-1 activity was measured by a spectrophotometric assay and PAI-1 4G/5G promoter genotype by the polymerase chain reaction (PCR) using allele-specific primers. Retinopathy was assessed by ophthalmoscopy after pupillary dilation and classified as any retinopathy or as nonproliferative and proliferative.

RESULTS

Retinopathy was present in 70 (41%) subjects, and 4 (2.3%) subjects had proliferative retinopathy. Plasma PAI-1 activity was not significantly different among subjects with and without retinopathy (17.1 +/- vs. 19.7 +/- 9.1 arbitrary units (AU)/ml, P = 0.09). PAI-1 activity was negatively correlated with duration of diabetes (rs = -0.18, P = 0.02). In a logistic regression analysis controlled for age, sex, BMI, and duration of diabetes, any retinopathy was significantly associated with fasting plasma glucose concentrations (P < 0.05), 2-h postload glucose (P = 0.02), and HbA1c (P = 0.008), but not with PAI-1 activity (P = 0.48). The prevalence of retinopathy in the three genotype groups differed significantly (4G/4G, 4G/5G, and 5G/5G were 44, 49, and 24%, respectively; chi 2 = 8.22, df = 2, P = 0.016) and remained significant after controlling for age, sex, BMI, duration of diabetes, glycated hemoglobin, and urine albumin-to-creatine ratio in a logistic regression analysis. The odds ratios for retinopathy in subjects with 4G/4G and 4G/5G, compared with the 5G/5G genotype, were 2.0 and 3.1, respectively.

CONCLUSIONS

Although diabetic retinopathy in Pima Indians with type 2 diabetes is not associated with PAI-1 activity, subjects with the 4G/4G and 4G/5G genotype had a higher prevalence of retinopathy compared with 5G/5G PAI-1genotype. These preliminary findings indicate that in Pima Indians with type 2 diabetes, presence of the 4G allele of the PAI-1 gene was associated with a higher risk of diabetic retinopathy.

Authors+Show Affiliations

National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

9250459

Citation

Nagi, D K., et al. "Diabetic Retinopathy, Promoter (4G/5G) Polymorphism of PAI-1 Gene, and PAI-1 Activity in Pima Indians With Type 2 Diabetes." Diabetes Care, vol. 20, no. 8, 1997, pp. 1304-9.
Nagi DK, McCormack LJ, Mohamed-Ali V, et al. Diabetic retinopathy, promoter (4G/5G) polymorphism of PAI-1 gene, and PAI-1 activity in Pima Indians with type 2 diabetes. Diabetes Care. 1997;20(8):1304-9.
Nagi, D. K., McCormack, L. J., Mohamed-Ali, V., Yudkin, J. S., Knowler, W. C., & Grant, P. J. (1997). Diabetic retinopathy, promoter (4G/5G) polymorphism of PAI-1 gene, and PAI-1 activity in Pima Indians with type 2 diabetes. Diabetes Care, 20(8), pp. 1304-9.
Nagi DK, et al. Diabetic Retinopathy, Promoter (4G/5G) Polymorphism of PAI-1 Gene, and PAI-1 Activity in Pima Indians With Type 2 Diabetes. Diabetes Care. 1997;20(8):1304-9. PubMed PMID: 9250459.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diabetic retinopathy, promoter (4G/5G) polymorphism of PAI-1 gene, and PAI-1 activity in Pima Indians with type 2 diabetes. AU - Nagi,D K, AU - McCormack,L J, AU - Mohamed-Ali,V, AU - Yudkin,J S, AU - Knowler,W C, AU - Grant,P J, PY - 1997/8/1/pubmed PY - 1997/8/1/medline PY - 1997/8/1/entrez SP - 1304 EP - 9 JF - Diabetes care JO - Diabetes Care VL - 20 IS - 8 N2 - OBJECTIVE: To examine the relationship between plasma plasminogen activator inhibitor 1 (PAI-1) activity and PAI-1 gene (4G/5G) polymorphism and diabetic retinopathy in Pima Indians with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 171 Pima Indians with type 2 diabetes between the ages of 30-70 years in a population-based epidemiological survey. Plasma PAI-1 activity was measured by a spectrophotometric assay and PAI-1 4G/5G promoter genotype by the polymerase chain reaction (PCR) using allele-specific primers. Retinopathy was assessed by ophthalmoscopy after pupillary dilation and classified as any retinopathy or as nonproliferative and proliferative. RESULTS: Retinopathy was present in 70 (41%) subjects, and 4 (2.3%) subjects had proliferative retinopathy. Plasma PAI-1 activity was not significantly different among subjects with and without retinopathy (17.1 +/- vs. 19.7 +/- 9.1 arbitrary units (AU)/ml, P = 0.09). PAI-1 activity was negatively correlated with duration of diabetes (rs = -0.18, P = 0.02). In a logistic regression analysis controlled for age, sex, BMI, and duration of diabetes, any retinopathy was significantly associated with fasting plasma glucose concentrations (P < 0.05), 2-h postload glucose (P = 0.02), and HbA1c (P = 0.008), but not with PAI-1 activity (P = 0.48). The prevalence of retinopathy in the three genotype groups differed significantly (4G/4G, 4G/5G, and 5G/5G were 44, 49, and 24%, respectively; chi 2 = 8.22, df = 2, P = 0.016) and remained significant after controlling for age, sex, BMI, duration of diabetes, glycated hemoglobin, and urine albumin-to-creatine ratio in a logistic regression analysis. The odds ratios for retinopathy in subjects with 4G/4G and 4G/5G, compared with the 5G/5G genotype, were 2.0 and 3.1, respectively. CONCLUSIONS: Although diabetic retinopathy in Pima Indians with type 2 diabetes is not associated with PAI-1 activity, subjects with the 4G/4G and 4G/5G genotype had a higher prevalence of retinopathy compared with 5G/5G PAI-1genotype. These preliminary findings indicate that in Pima Indians with type 2 diabetes, presence of the 4G allele of the PAI-1 gene was associated with a higher risk of diabetic retinopathy. SN - 0149-5992 UR - https://www.unboundmedicine.com/medline/citation/9250459/Diabetic_retinopathy_promoter__4G/5G__polymorphism_of_PAI_1_gene_and_PAI_1_activity_in_Pima_Indians_with_type_2_diabetes_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;PAGE=linkout&amp;SEARCH=9250459.ui DB - PRIME DP - Unbound Medicine ER -