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
- 1Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
- 2Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia
- 3School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
- 4Department of Molecular Genetics, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
- 5Department of Medicine (St. Vincent's), University of Melbourne, Melbourne, Victoria, Australia
- 6Department of Paediatrics, Medical University of Innsbruck, Innsbruck, Austria
- 7Department of Radiology, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
- Corresponding author: Patricia H. Gallego, 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 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.
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 9 May 2008.
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- Received November 25, 2007.
- Accepted May 2, 2008.
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