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Published online May 9, 2008
Diabetes Care 31:1585-1589, 2008
DOI: 10.2337/dc07-2236
© 2008 by the American Diabetes Association
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Pathophysiology/Complications
Original Research

Association Between p.Leu54Met Polymorphism at the Paraoxonase-1 Gene and Plantar Fascia Thickness in Young Subjects With Type 1 Diabetes

Patricia H. Gallego, MD, MSC1, Maria E. Craig, MBBS, PHD, FRACP1,2,3, Anthony C. Duffin, PHD1, Bruce Bennetts, PHD, FHGSA4, Alicia J. Jenkins, MBBS, MD, FRACP, FRCP5, Sabine Hofer, MD6, Albert Lam, MD, FRACR7 and Kim C. Donaghue, MBBS, PHD, FRACP1,2

1 Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
2 Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia
3 School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
4 Department of Molecular Genetics, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
5 Department of Medicine (St. Vincent's), University of Melbourne, Melbourne, Victoria, Australia
6 Department of Paediatrics, Medical University of Innsbruck, Innsbruck, Austria
7 Department of Radiology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia

Corresponding author: Patricia H. Gallego, patricg4{at}chw.edu.au

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 [1.01–1.03], 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.


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