Abstract
BackgroundHuman serum paraoxonase 1 (PON1) plays a major role in the metabolism of several organophosphorus compounds. The enzyme is encoded by the polymorphic gene PON1, located on chromosome 7q21.3. Aiming to identify genetic variations related to the risk of developing brain tumors, we investigated the putative association between common nonsynonymous PON1 polymorphisms and the risk of developing astrocytoma and meningioma.MethodsSeventy one consecutive patients with brain tumors (43 with astrocytoma grade II/III and 28 with meningioma) with ages ranging 21 to 76 years, and 220 healthy controls subjects were analyzed for the frequency of the nonsynonymous PON1 genotypes L55M rs854560 and Q192R rs662. All participants were adult Caucasian individuals recruited in the central area of Spain.ResultsThe frequencies of the PON1 genotypes and allelic variants of the polymorphisms PON1 L55M and PON1 Q192R did not differ significantly between patients with astrocytoma and meningioma and controls. The minor allele frequencies were as follows: PON1 55L, 0.398, 0.328 and 0.286 for patients with astrocytoma, meningioma and control individuals, respectively; PON1 192R, 0.341, 0.362 and 0.302 for patients with astrocytoma, meningioma and control individuals, respectively. Correction for age, gender, or education, made no difference in odds ratios and the p values remained non-significant. Haplotype association analyses did not identify any significant association with the risk of developing astrocytoma or meningioma.ConclusionsCommon nonsynonymous PON1 polymorphisms are not related with the risk of developing astrocytoma and meningioma.
Highlights
Human serum paraoxonase 1 (PON1) plays a major role in the metabolism of several organophosphorus compounds
Human serum paraoxonase 1 (PON1), a enzyme encoded by the polymorphic gene PON1 on chromosome 7q21.3, is an aryldialkylphosphatase, synthesized mainly in the liver, that plays a major role in the metabolism of several organophosphorus compounds, like some insecticides, neurotoxins, and arylesters [17]
All consecutive patients attending the participating hospitals (Hospital Universitario “Doce de Octubre” (Madrid, Spain) and the Hospital Universitario Infanta Cristina (Badajoz, Spain)) between 1997 and 1999 that were diagnosed of astrocytoma grade II/III or brain meningioma were included in the study, and none was excluded for any reason
Summary
Human serum paraoxonase 1 (PON1) plays a major role in the metabolism of several organophosphorus compounds. Aiming to identify genetic variations related to the risk of developing brain tumors, we investigated the putative association between common nonsynonymous PON1 polymorphisms and the risk of developing astrocytoma and meningioma. Human serum paraoxonase 1 (PON1), a enzyme encoded by the polymorphic gene PON1 on chromosome 7q21.3, is an aryldialkylphosphatase, synthesized mainly in the liver, that plays a major role in the metabolism of several organophosphorus compounds, like some insecticides, neurotoxins, and arylesters [17]. T > A according to the GenBank accession number NM 000446) and a glutamine to arginine substitution at position 192 PON1 is implicated in the elimination of carcinogenic lipid-soluble radicals from lipid peroxidation [27]
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