Dataset Information

Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea-induced hypoglycaemia: A GoDARTS Study.

ABSTRACT: Data on the association of CYP2C9 genetic polymorphisms with sulfonylurea (SU)-induced hypoglycaemia (SH) are inconsistent. Recent studies showed that variants in the P450 oxidoreductase (POR) gene could affect CYP2C9 activity. In this study, we explored the effects of POR*28 and combined CYP2C9*2 and CYP2C9*3 genotypes on SH and the efficacy of SU treatment in type 2 diabetes. A total of 1770 patients were included in the analysis of SU efficacy, assessed as the combined outcome of the HbA1c reduction and the prescribed SU daily dose. Sixty-nine patients with severe SH were compared with 311 control patients. The number of CYP2C9 deficient alleles was associated with nearly three-fold higher odds of hypoglycaemia (OR, 2.81; 95% CI, 1.30-6.09; P?=?.009) and better response to SU treatment (?, -0.218; SE, 0.074; P?=?.003) only in patients carrying the POR*1/*1 genotype. Our results indicate that interaction between CYP2C9 and POR genes may be an important determinant of efficacy and severe adverse effects of SU treatment.

SUBMITTER: Dujic T

PROVIDER: S-EPMC5724509 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea-induced hypoglycaemia: A GoDARTS Study.

Dujic Tanja T Zhou Kaixin K Donnelly Louise A LA Leese Graham G Palmer Colin N A CNA Pearson Ewan R ER

Diabetes, obesity & metabolism 20170825 1

Data on the association of CYP2C9 genetic polymorphisms with sulfonylurea (SU)-induced hypoglycaemia (SH) are inconsistent. Recent studies showed that variants in the P450 oxidoreductase (POR) gene could affect CYP2C9 activity. In this study, we explored the effects of POR*28 and combined CYP2C9*2 and CYP2C9*3 genotypes on SH and the efficacy of SU treatment in type 2 diabetes. A total of 1770 patients were included in the analysis of SU efficacy, assessed as the combined outcome of the HbA1c re ...[more]

PMID: 28656666

Similar Datasets

Project description:ObjectivesTo determine whether temporal patterns of hypoglycaemia exist in inpatients with diabetes 'at risk' of hypoglycaemia (those on insulin and/or sulfonylureas), and if so whether patterns differ between hospitals and between these treatments.SettingRetrospective multicentre audit of inpatients with diabetes involving 11 acute UK National Health Service (NHS) trusts.ParticipantsCapillary blood glucose readings of 3.9 mmol/L or less (hypoglycaemia) for all adult (≥18 years) inpatients with diabetes 'at risk' of hypoglycaemia were extracted from the Abbott PrecisionWeb Point-of-Care Data Management System over a 4-week period. Overall, 2521 readings of 3.9 mmol/L or less (hypoglycaemia) occurring in 866 participants between 1 June 2013 and 29 June 2013 were analysed.ResultsThe majority (65%) occurred between 21:00 and 08:59, a pattern common to all Trusts. This was more frequent in sulfonylurea-treated than insulin-treated participants (75.3% vs 59.3%, p=0.0001). Furthermore, hypoglycaemic readings were more frequent between 5:00 and 7:59 in sulfonylurea-treated than insulin-treated participants (46.7% vs 22.7% of readings for respective treatments, p=0.0001). Sulfonylureas accounted for 31.8% of all hypoglycaemic readings. As a group, sulfonylurea-treated participants were older (median age 78 vs 73 years, p=0.0001) and had lower glycated haemoglobin (median 56 (7.3%) vs 69 mmol/mol (8.5%), p=0.0001). Hypoglycaemic readings per participant were as frequent for sulfonylurea-treated participants as for insulin-treated participants (median=2 for both) as were the proportions in each group with ≥5 hypoglycaemic readings (17.3% vs 17.7%).ConclusionsIn all Trusts, hypoglycaemic readings were more frequent between 21:00 and 08:59 in 'at risk' inpatients with diabetes, with a greater frequency in the early morning period (5:00-7:59) in sulfonylurea-treated inpatients. This may have implications for the continuing use of sulfonylureas in the inpatient setting.

Dataset Information

Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea-induced hypoglycaemia: A GoDARTS Study.

Publications

Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea-induced hypoglycaemia: A GoDARTS Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets