Paraoxonase 1 gene polymorphisms in patients with osteonecrosis of the femoral head with and without cerebral white matter lesions.
Cerebral white matter lesions (WML) are present in more than 50% of patients with osteonecrosis of the femoral head (ONFH). Paraoxonase 1 (PON1) gene product is a detoxifying and pesticide metabolizing enzyme. Genetic variants of the PON1 gene have been found to influence the occurrence and progression of WML. We examined whether two PON1 polymorphisms (M55L and R192Q) are associated with ONFH and influence the occurrence of WML. We studied 104 patients with ONFH and 113 healthy age- and sex-matched subjects. We used logistic regression models to examine associations and survival analyses (Cox proportional hazards models) to examine possible influence of alleles on age at onset of ONFH. We found no association of PON1 M55L alleles and genotypes with ONFH. The distribution of PON1 Q192R alleles (p = 0.001) and genotypes (QQ vs. QR/RR) (p = 0.004) were statistically different between controls and patients. Patients with QQ genotype had six times higher risk for WML at brain MRI (adjusted OR 5.95; 95% CI 1.30-27.03; p = 0.02). In Cox models, there was a significant association of allele Q with risk for ONFH indicating a possible dose effect (HR = 1.43; 95%CI = 1.04-1.97; p for trend = 0.03). We conclude that individuals with PON1 192QQ genotype may have increased risk for ONFH and WMLeOn.
Hadjigeorgiou
Georgios M
GM
Neurogenetics Unit, Department of Neurology, School of Medicine, University of Thessaly, Larissa 41222, Greece. gmhadji@med.uth.gr
Malizos
Konstantinos
K
Dardiotis
Efthimios
E
Aggelakis
Konstantinos
K
Dardioti
Maria
M
Zibis
Aristidis
A
Dimitroulias
Apostolos
A
Scarmeas
Nikolaos
N
Tsezou
Aspasia
A
Karantanas
Apostolos
A
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D001927:Brain Diseases / Q000201:enzymology / Q000235:genetics*; D002540:Cerebral Cortex / Q000201:enzymology; D005260:Female; D005271:Femur Head Necrosis / Q000201:enzymology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D008055:Lipids; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human