title: Paraoxonase (PON)1 Q192R functional genotypes and PON1 Q192R genotype by smoking interactions are risk factors for the metabolic syndrome, but not overweight or obesity.
abstract: Background The metabolic syndrome (MetS) is a complex of multiple risk factors that contribute to the onset of cardiovascular disorder, including lowered levels of high-density lipoprotein (HDL) and abdominal obesity. Smoking, mood disorders, and oxidative stress are associated with the MetS. Paraoxonase (PON)1 is an antioxidant bound to HDL, that is under genetic control by functional polymorphisms in the PON1 Q192R coding sequence. Aims and methods This study aimed to delineate the associations of the MetS with plasma PON1 activity, PON1 Q192R genotypes, smoking, and mood disorders (major depression and bipolar disorder), while adjusting for HDL cholesterol, body mass index, age, gender, and sociodemographic data. We measured plasma PON1 activity and serum HDL cholesterol and determined PON1 Q192R genotypes through functional analysis in 335 subjects, consisting of 97 with and 238 without MetS. The severity of nicotine dependence was measured using the Fagerström Nicotine Dependence Scale. Results PON1 Q192R functional genotypes and PON1 Q192R genotypes by smoking interactions were associated with the MetS. The QQ and QR genotypes were protective against MetS while smoking increased metabolic risk in QQ carriers only. There were no significant associations between PON1 Q192R genotypes and smoking by genotype interactions and obesity or overweight, while body mass index significantly increased MetS risk. Smoking and especially severe nicotine dependence are significantly associated with the MetS although these effects were no longer significant after considering the effects of the smoking by PON1 Q192R genotype interaction. The MetS was not associated with mood disorders, major depression or bipolar disorder. Discussion PON1 Q192R genotypes and genotypes by smoking interactions are risk factors for the MetS that together with lowered HDL and increased body mass and age contribute to the MetS.
authors.forename: Chiara Cristina
authors.initials: CC
authors.lastname: Bortolasci
authors.forename: Heber Odebrecht
authors.initials: HO
authors.lastname: Vargas
authors.forename: André
authors.initials: A
authors.lastname: Souza-Nogueira
authors.forename: Estefania
authors.initials: E
authors.lastname: Gastaldello Moreira
authors.forename: Sandra Odebrecht
authors.initials: SO
authors.lastname: Vargas Nunes
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: Seetal
authors.initials: S
authors.lastname: Dodd
authors.forename: Décio Sabbatini
authors.initials: DS
authors.lastname: Barbosa
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
mesh_terms: D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000737:chemistry; D043303:Aryldialkylphosphatase / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000235:genetics; D003863:Depression / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006868:Hydrolysis; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D050177:Overweight / Q000235:genetics*; D018384:Oxidative Stress; D012307:Risk Factors; D012907:Smoking; D055815:Young Adult
chemical_list: D000975:Antioxidants; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Cardiovascular; Depression; HDL cholesterol; Metabolic syndrome; Oxidative stress; Paraoxonase 1