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


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.
Gallego
Patricia H
PH
Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia. patricg4@chw.edu.au
Craig
Maria E
ME
Duffin
Anthony C
AC
Bennetts
Bruce
B
Jenkins
Alicia J
AJ
Hofer
Sabine
S
Lam
Albert
A
Donaghue
Kim C
KC
D000293:Adolescent; D019943:Amino Acid Substitution; D001120:Arginine; D043303:Aryldialkylphosphatase / Q000235:genetics*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D036981:Fasciitis, Plantar / Q000150:complications / Q000473:pathology*; D005260:Female; D005973:Glutamine; D006801:Humans; D007930:Leucine; D008297:Male; D008715:Methionine; D009517:New South Wales; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
D005973:Glutamine; D001120:Arginine; D008715:Methionine; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D007930:Leucine