The gene-treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes: Fukuoka diabetes registry

Akiko Sumi, Udai Nakamura, Masanori Iwase, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Tamaki Jodai-Kitamura, Yuji Komorita, Masahito Yoshinari, Yoichiro Hirakawa, Atsushi Hirano, Michiaki Kubo, Takanari Kitazono

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Although statins deteriorate glucose metabolism, their glucose-lowering effects have emerged in some situations. Here, we assessed whether these effects are a consequence of statins' interaction with paraoxonase (PON)1 enzyme polymorphism. Methods: Adult Japanese type 2 diabetes patients (n=3798) were enrolled in a cross-sectional study. We used Q192R polymorphism of the PON1 gene as a representative single-nucleotide polymorphism and focused on the effects of the wild-type Q allele, in an additive manner. For patients with and without statin therapy, the associations of this allele with fasting plasma glucose (FPG), HbA1c, C-peptide, HOMA2-%β, and HOMA2-IR were investigated separately using a linear regression model, and were compared between groups by testing interactions. Sensitivity analyses were performed using propensity score to further control the imbalance of characteristics between groups. Results: Among patients with statin therapy, there were linear associations of the number of Q alleles with decreased FPG and HbA1c, and with increased serum C peptide and HOMA2-%β (all P<0.01 for trends), while such associations were not observed among those without statin therapy. These differences were statistically significant only for serum C peptide and HOMA2-%β (P<0.01 for interactions). These associations remained significant after multiple explanatory variable adjustment. Sensitivity analyses using propensity score showed broad consistency of these associations. Conclusions: Patients with the Q allele of the PON1 Q192R polymorphism who were treated with statins exhibited improvement in glucose metabolism, especially in insulin secretion, suggesting the importance of genotyping PON1 Q192R to identify those who could benefit from statin therapy.

Original languageEnglish
Article number146
JournalBMC Medical Genetics
Volume18
Issue number1
DOIs
Publication statusPublished - 12-12-2017

Fingerprint

Aryldialkylphosphatase
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Type 2 Diabetes Mellitus
Registries
Insulin
C-Peptide
Glucose
Genes
Alleles
Propensity Score
Therapeutics
Linear Models
Fasting
Social Adjustment
Serum
Single Nucleotide Polymorphism
Cross-Sectional Studies
Enzymes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Sumi, Akiko ; Nakamura, Udai ; Iwase, Masanori ; Fujii, Hiroki ; Ohkuma, Toshiaki ; Ide, Hitoshi ; Jodai-Kitamura, Tamaki ; Komorita, Yuji ; Yoshinari, Masahito ; Hirakawa, Yoichiro ; Hirano, Atsushi ; Kubo, Michiaki ; Kitazono, Takanari. / The gene-treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes : Fukuoka diabetes registry. In: BMC Medical Genetics. 2017 ; Vol. 18, No. 1.
@article{45f4c67a7fe24bd7b4522c3b2cf6b0e9,
title = "The gene-treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes: Fukuoka diabetes registry",
abstract = "Background: Although statins deteriorate glucose metabolism, their glucose-lowering effects have emerged in some situations. Here, we assessed whether these effects are a consequence of statins' interaction with paraoxonase (PON)1 enzyme polymorphism. Methods: Adult Japanese type 2 diabetes patients (n=3798) were enrolled in a cross-sectional study. We used Q192R polymorphism of the PON1 gene as a representative single-nucleotide polymorphism and focused on the effects of the wild-type Q allele, in an additive manner. For patients with and without statin therapy, the associations of this allele with fasting plasma glucose (FPG), HbA1c, C-peptide, HOMA2-{\%}β, and HOMA2-IR were investigated separately using a linear regression model, and were compared between groups by testing interactions. Sensitivity analyses were performed using propensity score to further control the imbalance of characteristics between groups. Results: Among patients with statin therapy, there were linear associations of the number of Q alleles with decreased FPG and HbA1c, and with increased serum C peptide and HOMA2-{\%}β (all P<0.01 for trends), while such associations were not observed among those without statin therapy. These differences were statistically significant only for serum C peptide and HOMA2-{\%}β (P<0.01 for interactions). These associations remained significant after multiple explanatory variable adjustment. Sensitivity analyses using propensity score showed broad consistency of these associations. Conclusions: Patients with the Q allele of the PON1 Q192R polymorphism who were treated with statins exhibited improvement in glucose metabolism, especially in insulin secretion, suggesting the importance of genotyping PON1 Q192R to identify those who could benefit from statin therapy.",
author = "Akiko Sumi and Udai Nakamura and Masanori Iwase and Hiroki Fujii and Toshiaki Ohkuma and Hitoshi Ide and Tamaki Jodai-Kitamura and Yuji Komorita and Masahito Yoshinari and Yoichiro Hirakawa and Atsushi Hirano and Michiaki Kubo and Takanari Kitazono",
year = "2017",
month = "12",
day = "12",
doi = "10.1186/s12881-017-0509-1",
language = "English",
volume = "18",
journal = "BMC Medical Genetics",
issn = "1471-2350",
publisher = "BioMed Central",
number = "1",

}

Sumi, A, Nakamura, U, Iwase, M, Fujii, H, Ohkuma, T, Ide, H, Jodai-Kitamura, T, Komorita, Y, Yoshinari, M, Hirakawa, Y, Hirano, A, Kubo, M & Kitazono, T 2017, 'The gene-treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes: Fukuoka diabetes registry', BMC Medical Genetics, vol. 18, no. 1, 146. https://doi.org/10.1186/s12881-017-0509-1

The gene-treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes : Fukuoka diabetes registry. / Sumi, Akiko; Nakamura, Udai; Iwase, Masanori; Fujii, Hiroki; Ohkuma, Toshiaki; Ide, Hitoshi; Jodai-Kitamura, Tamaki; Komorita, Yuji; Yoshinari, Masahito; Hirakawa, Yoichiro; Hirano, Atsushi; Kubo, Michiaki; Kitazono, Takanari.

In: BMC Medical Genetics, Vol. 18, No. 1, 146, 12.12.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The gene-treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes

T2 - Fukuoka diabetes registry

AU - Sumi, Akiko

AU - Nakamura, Udai

AU - Iwase, Masanori

AU - Fujii, Hiroki

AU - Ohkuma, Toshiaki

AU - Ide, Hitoshi

AU - Jodai-Kitamura, Tamaki

AU - Komorita, Yuji

AU - Yoshinari, Masahito

AU - Hirakawa, Yoichiro

AU - Hirano, Atsushi

AU - Kubo, Michiaki

AU - Kitazono, Takanari

PY - 2017/12/12

Y1 - 2017/12/12

N2 - Background: Although statins deteriorate glucose metabolism, their glucose-lowering effects have emerged in some situations. Here, we assessed whether these effects are a consequence of statins' interaction with paraoxonase (PON)1 enzyme polymorphism. Methods: Adult Japanese type 2 diabetes patients (n=3798) were enrolled in a cross-sectional study. We used Q192R polymorphism of the PON1 gene as a representative single-nucleotide polymorphism and focused on the effects of the wild-type Q allele, in an additive manner. For patients with and without statin therapy, the associations of this allele with fasting plasma glucose (FPG), HbA1c, C-peptide, HOMA2-%β, and HOMA2-IR were investigated separately using a linear regression model, and were compared between groups by testing interactions. Sensitivity analyses were performed using propensity score to further control the imbalance of characteristics between groups. Results: Among patients with statin therapy, there were linear associations of the number of Q alleles with decreased FPG and HbA1c, and with increased serum C peptide and HOMA2-%β (all P<0.01 for trends), while such associations were not observed among those without statin therapy. These differences were statistically significant only for serum C peptide and HOMA2-%β (P<0.01 for interactions). These associations remained significant after multiple explanatory variable adjustment. Sensitivity analyses using propensity score showed broad consistency of these associations. Conclusions: Patients with the Q allele of the PON1 Q192R polymorphism who were treated with statins exhibited improvement in glucose metabolism, especially in insulin secretion, suggesting the importance of genotyping PON1 Q192R to identify those who could benefit from statin therapy.

AB - Background: Although statins deteriorate glucose metabolism, their glucose-lowering effects have emerged in some situations. Here, we assessed whether these effects are a consequence of statins' interaction with paraoxonase (PON)1 enzyme polymorphism. Methods: Adult Japanese type 2 diabetes patients (n=3798) were enrolled in a cross-sectional study. We used Q192R polymorphism of the PON1 gene as a representative single-nucleotide polymorphism and focused on the effects of the wild-type Q allele, in an additive manner. For patients with and without statin therapy, the associations of this allele with fasting plasma glucose (FPG), HbA1c, C-peptide, HOMA2-%β, and HOMA2-IR were investigated separately using a linear regression model, and were compared between groups by testing interactions. Sensitivity analyses were performed using propensity score to further control the imbalance of characteristics between groups. Results: Among patients with statin therapy, there were linear associations of the number of Q alleles with decreased FPG and HbA1c, and with increased serum C peptide and HOMA2-%β (all P<0.01 for trends), while such associations were not observed among those without statin therapy. These differences were statistically significant only for serum C peptide and HOMA2-%β (P<0.01 for interactions). These associations remained significant after multiple explanatory variable adjustment. Sensitivity analyses using propensity score showed broad consistency of these associations. Conclusions: Patients with the Q allele of the PON1 Q192R polymorphism who were treated with statins exhibited improvement in glucose metabolism, especially in insulin secretion, suggesting the importance of genotyping PON1 Q192R to identify those who could benefit from statin therapy.

UR - http://www.scopus.com/inward/record.url?scp=85037994887&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037994887&partnerID=8YFLogxK

U2 - 10.1186/s12881-017-0509-1

DO - 10.1186/s12881-017-0509-1

M3 - Article

C2 - 29233102

AN - SCOPUS:85037994887

VL - 18

JO - BMC Medical Genetics

JF - BMC Medical Genetics

SN - 1471-2350

IS - 1

M1 - 146

ER -