title: Relationships between polymorphisms of the human serum paraoxonase gene and insulin sensitivity in Japanese patients with type 2 diabetes.
abstract: Human serum paraoxonase (PON1), which is associated with HDL, is an esterase and has been shown to reduce the susceptibility of LDL to lipid peroxidation. The objective of the study was to determine whether genetic polymorphisms of the PON1 gene are associated with insulin sensitivity. Forty-eight Japanese patients with type 2 diabetes were recruited, and euglycemic hyperinsulinemic clamp was performed to assess insulin sensitivity. The PON1 promoter polymorphism C(-108)T was determined by direct sequencing, and the coding region polymorphism Q192R was determined by polymerase chain reaction and digestion of the amplified fragments. No association was observed between the Q192R polymorphism and the glucose infusion rate (GIR), whereas GIR increased with the following order of genotypes: -108TT < -108CT < and -108CC (4.2+/-1.6, 5.1+/-2.5, and 6.9+/-2.5 mg kg(-1) min(-1), respectively; P<0.02, ANCOVA). Stepwise regression analysis revealed that the C(-108)T polymorphism significantly contributed to the GIR. It has been reported that oxidative stress attenuates insulin signaling in vitro. The PON1 promoter polymorphism C(-108)T may influence insulin sensitivity by modulating serum antioxidant capacity.
authors.affiliation: Second Department of Internal Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Japan. ikeday@kochi-ms.ac.jp
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Suehiro
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ohsaki
authors.forename: Kaoru
authors.initials: K
authors.lastname: Arii
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Kumon
authors.forename: Kozo
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D019943:Amino Acid Substitution; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D044466:Asian People; D001483:Base Sequence; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005215:Fasting; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012044:Regression Analysis
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017931:DNA Primers; D007328:Insulin; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human