Association between p.Leu54Met polymorphism at the paraoxonase-1 gene and plantar fascia thickness in young subjects with type 1 diabetes

Abstract

OBJECTIVE -In type 1 diabetes, plantar fascia, a collagen-rich tissue, is susceptible to glycation and oxidation. Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme. PON1 polymorphisms have been associated with susceptibility to macro- and microvascular complications. We investigated the relationship between plantar fascia thickness (PFT) and PON1 gene variants, p.Leu54Met, p.Gln192Arg, and c.-107C>T, in type 1 diabetes. RESEARCH DESIGN AND METHODS - This was a cross-sectional study of 331 adolescents with type 1 diabetes (162 male and 169 female). PFT was assessed by ultrasound, PON1 was assessed by genotyping with PCR and restriction fragment-length polymorphism, and serum PON1 activity was assessed by rates of hydrolysis of paraoxon and phenylacetate. RESULTS- Median (interquartile range) age was 15.4 (13.5-17.3) years, and diabetes duration was 7.6 (4.9-10.6) years. The distribution of p.Leu54Met genotypes was LL 135 (40.8%), ML 149 (45%), and MM 47 (14.2%). PFT was abnormal (> 1.7 mm) in 159 adolescents (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL versus MM p.Leu54Met polymorphism (odds ratio 3.84 [95% CI 1.49-9.82], P = 0.005); BMI (percentile) (1.02 [1.011.03], P = 0.007); systolic blood pressure (percentile) (1.01 [1.00-1.02], P = 0.03); and male sex (3.29 [1.98-5.46], P < 0.001). CONCLUSIONS - Thickening of the plantar aponeurosis occurs predominantly in overweight and male adolescents with type 1 diabetes. The MM genotype at PON1 p.Leu54Met is associated with a reduced risk of abnormal PFT. © 2008 by the American Diabetes Association.