Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis
BackgroundVariants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies investigating the effect of OCT genetic polymorphisms on metformin response have reported inconsistent results. This review and met...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-07-01
|
| Series: | Frontiers in Public Health |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fpubh.2023.1183879/full |
| _version_ | 1797775575842029568 |
|---|---|
| author | Aiyu Peng Aiyu Peng Aiyu Peng Chunmei Gong Yuanfei Xu Xiongshun Liang Xiaoping Chen Wenxu Hong Junxia Yan Junxia Yan |
| author_facet | Aiyu Peng Aiyu Peng Aiyu Peng Chunmei Gong Yuanfei Xu Xiongshun Liang Xiaoping Chen Wenxu Hong Junxia Yan Junxia Yan |
| author_sort | Aiyu Peng |
| collection | DOAJ |
| description | BackgroundVariants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies investigating the effect of OCT genetic polymorphisms on metformin response have reported inconsistent results. This review and meta-analysis aimed to evaluate the associations between OCT genetic polymorphisms and metformin response and intolerance in individuals with type 2 diabetes mellitus (T2DM).MethodA systematic search was conducted on PubMed, EMBASE, CNKI, WANFANG DATA, and VIP database for identifying potential studies up to 10 November 2022. The Q-Genie tool was used to evaluate the quality of included studies. Pooled odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated to determine the associations between OCT genetic polymorphisms and metformin response and intolerance that were reflected by glycemic response indexes, such as glycated hemoglobin level (HbA1c%) or change in glycated hemoglobin level (ΔHbA1c%), fasting plasma level (FPG) or change in fasting plasma glucose level (ΔFPG), the effectiveness rate of metformin treatment, and the rate of metformin intolerance. A qualitative review was performed for the variants identified just in one study and those that could not undergo pooling analysis.ResultsA total of 30 related eligible studies about OCT genes (SLC22A1, SLC22A2, and SLC22A3) and metformin pharmacogenetics were identified, and 14, 3, and 6 single nucleotide polymorphisms (SNPs) in SLC22A1, SLC22A2, and SLC22A3, respectively, were investigated. Meta-analysis showed that the SLC22A1 rs622342 polymorphism was associated with a reduction in HbA1c level (AA vs. AC: SMD [95% CI] = −0.45 [−0.73–−0.18]; p = 0.001). The GG genotype of the SLC22A1 rs628031 polymorphism was associated with a reduction in FPG level (GG vs. AA: SMD [95 %CI] = −0.60 [−1.04–0.16], p = 0.007; GG vs. AG: −0.45 [−0.67–0.20], p < 0.001). No statistical association was found between the remaining variants and metformin response and intolerance.ConclusionSLC22A1 rs622342 and rs628031 polymorphisms were potentially associated with glycemic response to metformin. This evidence may provide novel insight into gene-oriented personalized medicine for diabetes. |
| first_indexed | 2024-03-12T22:37:38Z |
| format | Article |
| id | doaj.art-b0c111f5a71349c2b9aa461fef15cc57 |
| institution | Directory Open Access Journal |
| issn | 2296-2565 |
| language | English |
| last_indexed | 2024-03-12T22:37:38Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Public Health |
| spelling | doaj.art-b0c111f5a71349c2b9aa461fef15cc572023-07-21T11:33:31ZengFrontiers Media S.A.Frontiers in Public Health2296-25652023-07-011110.3389/fpubh.2023.11838791183879Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysisAiyu Peng0Aiyu Peng1Aiyu Peng2Chunmei Gong3Yuanfei Xu4Xiongshun Liang5Xiaoping Chen6Wenxu Hong7Junxia Yan8Junxia Yan9Animal Laboratory, Shenzhen Center for Chronic Disease Control, Shenzhen, ChinaDepartment of Epidemiology and Health Statistics, XiangYa School of Public Health, Central South University, Changsha, ChinaHunan Provincial Key Laboratory of Clinical Epidemiology, XiangYa School of Public Health, Central South University, Changsha, ChinaAnimal Laboratory, Shenzhen Center for Chronic Disease Control, Shenzhen, ChinaAnimal Laboratory, Shenzhen Center for Chronic Disease Control, Shenzhen, ChinaAnimal Laboratory, Shenzhen Center for Chronic Disease Control, Shenzhen, ChinaInstitute of Clinical Pharmacology, Central South University, Changsha, ChinaAnimal Laboratory, Shenzhen Center for Chronic Disease Control, Shenzhen, ChinaDepartment of Epidemiology and Health Statistics, XiangYa School of Public Health, Central South University, Changsha, ChinaHunan Provincial Key Laboratory of Clinical Epidemiology, XiangYa School of Public Health, Central South University, Changsha, ChinaBackgroundVariants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies investigating the effect of OCT genetic polymorphisms on metformin response have reported inconsistent results. This review and meta-analysis aimed to evaluate the associations between OCT genetic polymorphisms and metformin response and intolerance in individuals with type 2 diabetes mellitus (T2DM).MethodA systematic search was conducted on PubMed, EMBASE, CNKI, WANFANG DATA, and VIP database for identifying potential studies up to 10 November 2022. The Q-Genie tool was used to evaluate the quality of included studies. Pooled odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated to determine the associations between OCT genetic polymorphisms and metformin response and intolerance that were reflected by glycemic response indexes, such as glycated hemoglobin level (HbA1c%) or change in glycated hemoglobin level (ΔHbA1c%), fasting plasma level (FPG) or change in fasting plasma glucose level (ΔFPG), the effectiveness rate of metformin treatment, and the rate of metformin intolerance. A qualitative review was performed for the variants identified just in one study and those that could not undergo pooling analysis.ResultsA total of 30 related eligible studies about OCT genes (SLC22A1, SLC22A2, and SLC22A3) and metformin pharmacogenetics were identified, and 14, 3, and 6 single nucleotide polymorphisms (SNPs) in SLC22A1, SLC22A2, and SLC22A3, respectively, were investigated. Meta-analysis showed that the SLC22A1 rs622342 polymorphism was associated with a reduction in HbA1c level (AA vs. AC: SMD [95% CI] = −0.45 [−0.73–−0.18]; p = 0.001). The GG genotype of the SLC22A1 rs628031 polymorphism was associated with a reduction in FPG level (GG vs. AA: SMD [95 %CI] = −0.60 [−1.04–0.16], p = 0.007; GG vs. AG: −0.45 [−0.67–0.20], p < 0.001). No statistical association was found between the remaining variants and metformin response and intolerance.ConclusionSLC22A1 rs622342 and rs628031 polymorphisms were potentially associated with glycemic response to metformin. This evidence may provide novel insight into gene-oriented personalized medicine for diabetes.https://www.frontiersin.org/articles/10.3389/fpubh.2023.1183879/fullorganic cation transportersgenetic polymorphismstype 2 diabetes mellitusmetformin responsemetformin intolerance |
| spellingShingle | Aiyu Peng Aiyu Peng Aiyu Peng Chunmei Gong Yuanfei Xu Xiongshun Liang Xiaoping Chen Wenxu Hong Junxia Yan Junxia Yan Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis Frontiers in Public Health organic cation transporters genetic polymorphisms type 2 diabetes mellitus metformin response metformin intolerance |
| title | Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis |
| title_full | Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis |
| title_fullStr | Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis |
| title_full_unstemmed | Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis |
| title_short | Association between organic cation transporter genetic polymorphisms and metformin response and intolerance in T2DM individuals: a systematic review and meta-analysis |
| title_sort | association between organic cation transporter genetic polymorphisms and metformin response and intolerance in t2dm individuals a systematic review and meta analysis |
| topic | organic cation transporters genetic polymorphisms type 2 diabetes mellitus metformin response metformin intolerance |
| url | https://www.frontiersin.org/articles/10.3389/fpubh.2023.1183879/full |
| work_keys_str_mv | AT aiyupeng associationbetweenorganiccationtransportergeneticpolymorphismsandmetforminresponseandintoleranceint2dmindividualsasystematicreviewandmetaanalysis AT aiyupeng associationbetweenorganiccationtransportergeneticpolymorphismsandmetforminresponseandintoleranceint2dmindividualsasystematicreviewandmetaanalysis AT aiyupeng associationbetweenorganiccationtransportergeneticpolymorphismsandmetforminresponseandintoleranceint2dmindividualsasystematicreviewandmetaanalysis AT chunmeigong associationbetweenorganiccationtransportergeneticpolymorphismsandmetforminresponseandintoleranceint2dmindividualsasystematicreviewandmetaanalysis AT yuanfeixu associationbetweenorganiccationtransportergeneticpolymorphismsandmetforminresponseandintoleranceint2dmindividualsasystematicreviewandmetaanalysis AT xiongshunliang associationbetweenorganiccationtransportergeneticpolymorphismsandmetforminresponseandintoleranceint2dmindividualsasystematicreviewandmetaanalysis AT xiaopingchen associationbetweenorganiccationtransportergeneticpolymorphismsandmetforminresponseandintoleranceint2dmindividualsasystematicreviewandmetaanalysis AT wenxuhong associationbetweenorganiccationtransportergeneticpolymorphismsandmetforminresponseandintoleranceint2dmindividualsasystematicreviewandmetaanalysis AT junxiayan associationbetweenorganiccationtransportergeneticpolymorphismsandmetforminresponseandintoleranceint2dmindividualsasystematicreviewandmetaanalysis AT junxiayan associationbetweenorganiccationtransportergeneticpolymorphismsandmetforminresponseandintoleranceint2dmindividualsasystematicreviewandmetaanalysis |