title: Associations of xenobiotic-metabolizing enzyme genotypes PON1Q192R, PON1L55M and CYP1A1*2A MspI with pathological symptoms of a rural population in south Greece.
abstract: Paraoxonases and cytochromes P450 constitute two major classes of xenobiotic-metabolizing enzymes involved in the detoxification of pesticide chemicals. In this study, we examined the distribution of two common genetic polymorphisms of the paraoxonase 1 gene and one common polymorphism of the CYP1A1 gene, in relation to pathological diseases occurring in a rural population. Blood and hair samples were collected from 220 participants of an agricultural cohort in the south of Greece for genotype and pesticide analysis. Demographic information and disease status of the participants was obtained by questionnaire, medical examination and medical record. Organochlorine pesticides and metabolites (DDTs, HCHs) were extracted from hair and analyzed using gas chromatography combined with mass spectrometry techniques. Our results indicate exposure of the rural population of Amaliada to organophosphate and past exposure to organochlorine pesticides. Genotypic analysis of PON1Q192R, PON1L55M and CYP1A1*2A MspI polymorphisms was performed using PCR-RFLP. The PON1 192R and 55M alleles absence was significantly associated with hypertension (OR: 2.59; 95% CI: 1.10-6.09) and hepatitis (OR: 21.43; 95% CI: 2.53-181.50), respectively, as indicated from backward logistic regression. Although the presence of PON1 192R allele significantly affected the occurrence of prostate hyperplasia (OR: 0.35; 95% CI: 0.03-0.40), no associations were obtained between the paraoxonase serum activity or the CYP1A1 genotype and the disease status.
authors: University of Crete, Laboratory of Toxicology, Medical School, Heraklion, Crete, Greece. aris@med.uoc.gr
authors: Aristidis M
authors: AM
authors: Tsatsakis
authors: Vasilis P
authors: VP
authors: Androutsopoulos
authors: Alexandros
authors: A
authors: Zafiropoulos
authors: Fotoula
authors: F
authors: Babatsikou
authors: Thanasis
authors: T
authors: Alegakis
authors: Ioanna
authors: I
authors: Dialyna
authors: Manolis
authors: M
authors: Tzatzarakis
authors: Charilaos
authors: C
authors: Koutis
mesh_terms: D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D015331:Cohort Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D003920:Diabetes Mellitus / Q000453:epidemiology; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006115:Greece; D006506:Hepatitis A / Q000453:epidemiology; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D006973:Hypertension / Q000453:epidemiology; D008658:Inactivation, Metabolic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D010575:Pesticides / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D011110:Polymorphism, Genetic; D015995:Prevalence; D011470:Prostatic Hyperplasia / Q000453:epidemiology; D015262:Xenobiotics / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated; D010755:Organophosphates; D010575:Pesticides; D015262:Xenobiotics; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human