DOI: 10.2337/dc07-2236
Association between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects with Type 1 Diabetes
1Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, NSW Australia PatricG4{at}chw.edu.au 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 anti-oxidant enzyme. PON1 polymorphisms have been associated with macro and microvascular complication susceptibility. 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: Cross-sectional study of 331 adolescents with type 1 diabetes (162 M; 169 F). PFT was assessed by ultrasound; PON1 genotyping by PCR and restriction fragment length polymorphism (RFLP); serum PON1 activity by rates of hydrolysis of paraoxon and phenylacetate. Results: Median [interquartile range] age was 15.4 yrs [13.5 – 17.3] and diabetes duration was 7.6 yrs [ 4.9 – 10.6] . The distribution of p.Leu54Met genotypes was LL 135 (40.8%); ML 149 (45%) and MM 47 (14.2%). PFT was abnormal (>1.7mm) in 159 (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL vs MM p.Leu54Met polymorphism (OR, [95% CI] 3.84 [1.49 – 9.82], p=0.005; BMI (percentile) 1.02, [1.01 – 1.03], p=0.007 and SBP (percentile) 1.01, [1.00 – 1.02], p=0.03; male gender 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 reduced risk of abnormal PFT.
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