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 p...
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BMC
2017-12-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12881-017-0509-1 |
| _version_ | 1818948511316574208 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Akiko Sumi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T08:47:58Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-20T08:47:58Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
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| series | BMC Medical Genetics |
| spelling | doaj.art-7032e699cc4146bb96436cfbd1da03962022-12-21T19:46:12ZengBMCBMC Medical Genetics1471-23502017-12-011811810.1186/s12881-017-0509-1The gene–treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes: Fukuoka diabetes registryAkiko Sumi0Udai Nakamura1Masanori Iwase2Hiroki Fujii3Toshiaki Ohkuma4Hitoshi Ide5Tamaki Jodai-Kitamura6Yuji Komorita7Masahito Yoshinari8Yoichiro Hirakawa9Atsushi Hirano10Michiaki Kubo11Takanari Kitazono12Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityCentre for Cohort Studies, Graduate School of Medical Sciences Kyushu UniversityDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityEpidemiology and Public Health, Graduate School of Medical Sciences, Kyushu UniversityDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityCenter for Integrative Medical Sciences, RIKENDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu UniversityAbstract 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.http://link.springer.com/article/10.1186/s12881-017-0509-1Gene–treatment interactionPON1 Q192R polymorphismStatin therapyInsulin secretion |
| spellingShingle | 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 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 Gene–treatment interaction PON1 Q192R polymorphism Statin therapy Insulin secretion |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | gene treatment interaction of paraoxonase 1 gene polymorphism and statin therapy on insulin secretion in japanese patients with type 2 diabetes fukuoka diabetes registry |
| topic | Gene–treatment interaction PON1 Q192R polymorphism Statin therapy Insulin secretion |
| url | http://link.springer.com/article/10.1186/s12881-017-0509-1 |
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