RS11212617 is associated with metformin treatment response in type 2 diabetes in Shanghai local Chinese population

Zhou, Yong; Guo, Yu; Ye, W.; Wang, Y.; Li, X.; Tian, Ye; Liu, Z.; Li, S.; Jin, Yan

doi:10.1111/ijcp.12534

Cited by 31 publications

(30 citation statements)

References 17 publications

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“…The only GWAS of any antidiabetic agent published to date identified a variant rs11212617 near the ATM locus being associated with glycaemic response to metformin 39 . Independent replications were later reported in multiple cohorts of different ancestries, strengthening the evidence that the variant is the most established drug response variant for antidiabetic drug 62,63 . Given the moderate impact on glycaemic response to metformin, this variant is not a useful biomarker that can substantially increase our ability to accurately predict the treatment outcome in individual patients.…”

Section: Treatment Efficacymentioning

confidence: 73%

Pharmacogenomics in diabetes mellitus: insights into drug action and drug discovery

et al. 2016

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Genomic studies have greatly advanced our understanding of the multifactorial aetiology of type 2 diabetes mellitus (T2DM) as well as the multiple subtypes of monogenic diabetes mellitus. In this Review, we discuss the existing pharmacogenetic evidence in both monogenic diabetes mellitus and T2DM. We highlight mechanistic insights from the study of adverse effects and the efficacy of antidiabetic drugs. The identification of extreme sulfonylurea sensitivity in patients with diabetes mellitus owing to heterozygous mutations in HNF1A represents a clear example of how pharmacogenetics can direct patient care. However, pharmacogenomic studies of response to antidiabetic drugs in T2DM has yet to be translated into clinical practice, although some moderate genetic effects have now been described that merit follow-up in trials in which patients are selected according to genotype. We also discuss how future pharmacogenomic findings could provide insights into treatment response in diabetes mellitus that, in addition to other areas of human genetics, facilitates drug discovery and drug development for T2DM.

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Section: Treatment Efficacymentioning

confidence: 73%

Pharmacogenomics in diabetes mellitus: insights into drug action and drug discovery

et al. 2016

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“…46 In another study of 24 adult Native American kidney transplant recipients, CYP3A5*3 had a higher AF (0.94). 7 CYP3A5*3 is the most-studied CYP3A5 variant in association with tacrolimus and has been evaluated in Europeans, 18,21,[47][48][49][50][51][52] African Americans, 5,24,35,53 Asians, 52,[54][55][56][57][58][59][60] and Native Americans. Allele Frequency…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus troughs and genetic determinants of metabolism in kidney transplant recipients: A comparison of four ancestry groups

Mohamed

Schladt

Guan

et al. 2019

American Journal of Transplantation

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Tacrolimus trough and dose requirements vary dramatically between individuals ofEuropean and African American ancestry. These differences are less well described in other populations. We conducted an observational, prospective, multicenter study from which 2595 kidney transplant recipients of European, African, Native American, and Asian ancestry were studied for tacrolimus trough, doses, and genetic determinants of metabolism. We studied the well-known variants and conducted a CYP3A4/5 gene-wide analysis to identify new variants. Daily doses, and dose-normalized troughs were significantly different between the four groups (P < .001). CYP3A5*3 (rs776746) was associated with higher dose-normalized tacrolimus troughs in all groups but occurred at different allele frequencies and had differing effect sizes. The CYP3A5*6 (rs10264272) and *7 (rs413003343) variants were only present in African Americans. CYP3A4*22 (rs35599367) was not found in any of the Asian ancestry samples. We identified seven suggestive variants in the CYP3A4/5 genes associated with dose-normalized troughs in Native Americans (P = 1.1 × 10 −5 -8.8 × 10 −6 ) and

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“…This locus was subsequently replicated in two independent cohorts, including the UKPDS, with a combined overall P value = 2.9*10 ‐9 . This genetic association has been subsequently replicated in additional European cohorts and a Chinese cohort , making this the most robust metformin pharmacogenetic variant for metformin efficacy to date. The locus on chromosome 11, tagged by rs11212617, consists of a large LD block encompassing seven genes.…”

Section: Insights From Genome‐wide Studiesmentioning

confidence: 78%

Personalized medicine in diabetes: the role of ‘omics’ and biomarkers

Pearson

2016

Diabet. Med.

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Personalized medicine, otherwise called stratified or precision medicine, aims to better target intervention to the individual to maximize benefit and minimize harm. This review discusses how diabetes aetiology, pathophysiology and patient genotype influence response to or side effects of the commonly used diabetes treatments. C‐peptide is a useful biomarker that is underused to guide treatment choice, severe insulin deficiency predicts non‐response to glucagon‐like peptide‐1 receptor agonists, and thiazolidinediones are more effective in insulin‐resistant patients. The field of pharmacogenetics is now yielding clinically important results, with three examples outlined: sulphonylurea sensitivity in patients with HNF1A maturity‐onset diabetes of the young; sulphonylurea sensitivity in patients with Type 2 diabetes with reduced function alleles at CYP2C9, resulting in reduced metabolism of sulphonylureas; and severe metformin intolerance associated with reduced function organic cation transporter 1 (OCT1) variants, exacerbated by drugs that also inhibit OCT1. Genome‐wide approaches and the potential of other ‘omics’, including metagenomics and metabolomics, are then outlined, highlighting the complex interacting networks that we need to understand before we can truly personalize diabetes treatments.

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RS11212617 is associated with metformin treatment response in type 2 diabetes in Shanghai local Chinese population

Abstract: The rs11212617 is associated with a reduction in HbA1c, fasting plasma glucose and postprandial glucose level. These results suggest that metformin treatment may be more efficacious in Shanghai and valuable for Chinese daily clinical practice.

Cited by 31 publications

References 17 publications

Pharmacogenomics in diabetes mellitus: insights into drug action and drug discovery

Pharmacogenomics in diabetes mellitus: insights into drug action and drug discovery

Tacrolimus troughs and genetic determinants of metabolism in kidney transplant recipients: A comparison of four ancestry groups

Personalized medicine in diabetes: the role of ‘omics’ and biomarkers

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