The Membrane Transporter OAT7 (SLC22A9) Is Not a Susceptibility Factor for Osteoporosis in Europeans
Bone production, maintenance, and modeling are a well-balanced process involving mineralization by osteoblasts and resorption by osteoclasts. Sex steroid hormones, including their conjugated forms, contribute majorly to maintaining this balance. Recently, variants in the SLC22A9 gene have been assoc...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-08-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2020.00532/full |
| _version_ | 1811332693285142528 |
|---|---|
| author | Anne T. Nies Anne T. Nies Stefan Weiss Stefan Weiss Elke Schaeffeler Elke Schaeffeler Anke Hannemann Anke Hannemann Uwe Völker Uwe Völker Henri Wallaschofski Matthias Schwab Matthias Schwab Matthias Schwab |
| author_facet | Anne T. Nies Anne T. Nies Stefan Weiss Stefan Weiss Elke Schaeffeler Elke Schaeffeler Anke Hannemann Anke Hannemann Uwe Völker Uwe Völker Henri Wallaschofski Matthias Schwab Matthias Schwab Matthias Schwab |
| author_sort | Anne T. Nies |
| collection | DOAJ |
| description | Bone production, maintenance, and modeling are a well-balanced process involving mineralization by osteoblasts and resorption by osteoclasts. Sex steroid hormones, including their conjugated forms, contribute majorly to maintaining this balance. Recently, variants in the SLC22A9 gene have been associated with osteoporosis in Korean females. We had recently shown that SLC22A9, encoding organic anion transporter 7 (OAT7), is an uptake transporter of estrone sulfate and identified several genetic variants in Europeans leading to functional consequences in vitro. We therefore hypothesized that SLC22A9 genetic variants may contribute to the pathophysiology of osteoporosis in Europeans. To test this hypothesis, we examined the associations of SLC22A9 variants with bone quality, fractures, and bone turnover markers. We genotyped SLC22A9 variants in 5,701 (2,930 female) subjects (age range, 20–93 years) extracted from the population-based Study of Health in Pomerania (SHIP and SHIP-TREND) covered by the Illumina Infinium HumanExome BeadChip version v1.0 (Exome Chip). Descriptive data (e.g., history of fractures), ultrasonography of the calcaneus, as well as serum concentrations of carboxy-terminal telopeptide of type I collagen, amino-terminal propeptide of type I procollagen, and vitamin D were determined. Comprehensive statistical analyses revealed no association between low-frequency and rare SLC22A9 variants and bone quality, fractures, and bone turnover markers. Our results indicate that single genetic SLC22A9 variants do not have a major impact on osteoporosis risk prediction in Europeans, yet findings need to be replicated in larger-scale studies. |
| first_indexed | 2024-04-13T16:40:49Z |
| format | Article |
| id | doaj.art-4f0f6846f2894ac98bc2954821ad7665 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T16:40:49Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-4f0f6846f2894ac98bc2954821ad76652022-12-22T02:39:14ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922020-08-011110.3389/fendo.2020.00532548437The Membrane Transporter OAT7 (SLC22A9) Is Not a Susceptibility Factor for Osteoporosis in EuropeansAnne T. Nies0Anne T. Nies1Stefan Weiss2Stefan Weiss3Elke Schaeffeler4Elke Schaeffeler5Anke Hannemann6Anke Hannemann7Uwe Völker8Uwe Völker9Henri Wallaschofski10Matthias Schwab11Matthias Schwab12Matthias Schwab13Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, GermanyUniversity of Tübingen, Tübingen, GermanyInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald and University of Greifswald, Greifswald, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, GermanyUniversity of Tübingen, Tübingen, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, GermanyInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald and University of Greifswald, Greifswald, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, GermanyUniversity of Tübingen, Tübingen, GermanyDepartments of Clinical Pharmacology, Pharmacy and Biochemistry, University of Tübingen, Tübingen, GermanyBone production, maintenance, and modeling are a well-balanced process involving mineralization by osteoblasts and resorption by osteoclasts. Sex steroid hormones, including their conjugated forms, contribute majorly to maintaining this balance. Recently, variants in the SLC22A9 gene have been associated with osteoporosis in Korean females. We had recently shown that SLC22A9, encoding organic anion transporter 7 (OAT7), is an uptake transporter of estrone sulfate and identified several genetic variants in Europeans leading to functional consequences in vitro. We therefore hypothesized that SLC22A9 genetic variants may contribute to the pathophysiology of osteoporosis in Europeans. To test this hypothesis, we examined the associations of SLC22A9 variants with bone quality, fractures, and bone turnover markers. We genotyped SLC22A9 variants in 5,701 (2,930 female) subjects (age range, 20–93 years) extracted from the population-based Study of Health in Pomerania (SHIP and SHIP-TREND) covered by the Illumina Infinium HumanExome BeadChip version v1.0 (Exome Chip). Descriptive data (e.g., history of fractures), ultrasonography of the calcaneus, as well as serum concentrations of carboxy-terminal telopeptide of type I collagen, amino-terminal propeptide of type I procollagen, and vitamin D were determined. Comprehensive statistical analyses revealed no association between low-frequency and rare SLC22A9 variants and bone quality, fractures, and bone turnover markers. Our results indicate that single genetic SLC22A9 variants do not have a major impact on osteoporosis risk prediction in Europeans, yet findings need to be replicated in larger-scale studies.https://www.frontiersin.org/article/10.3389/fendo.2020.00532/fullestrone sulfate transporterSLC22A9osteoporosishuman association studiessex steroids |
| spellingShingle | Anne T. Nies Anne T. Nies Stefan Weiss Stefan Weiss Elke Schaeffeler Elke Schaeffeler Anke Hannemann Anke Hannemann Uwe Völker Uwe Völker Henri Wallaschofski Matthias Schwab Matthias Schwab Matthias Schwab The Membrane Transporter OAT7 (SLC22A9) Is Not a Susceptibility Factor for Osteoporosis in Europeans Frontiers in Endocrinology estrone sulfate transporter SLC22A9 osteoporosis human association studies sex steroids |
| title | The Membrane Transporter OAT7 (SLC22A9) Is Not a Susceptibility Factor for Osteoporosis in Europeans |
| title_full | The Membrane Transporter OAT7 (SLC22A9) Is Not a Susceptibility Factor for Osteoporosis in Europeans |
| title_fullStr | The Membrane Transporter OAT7 (SLC22A9) Is Not a Susceptibility Factor for Osteoporosis in Europeans |
| title_full_unstemmed | The Membrane Transporter OAT7 (SLC22A9) Is Not a Susceptibility Factor for Osteoporosis in Europeans |
| title_short | The Membrane Transporter OAT7 (SLC22A9) Is Not a Susceptibility Factor for Osteoporosis in Europeans |
| title_sort | membrane transporter oat7 slc22a9 is not a susceptibility factor for osteoporosis in europeans |
| topic | estrone sulfate transporter SLC22A9 osteoporosis human association studies sex steroids |
| url | https://www.frontiersin.org/article/10.3389/fendo.2020.00532/full |
| work_keys_str_mv | AT annetnies themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT annetnies themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT stefanweiss themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT stefanweiss themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT elkeschaeffeler themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT elkeschaeffeler themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT ankehannemann themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT ankehannemann themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT uwevolker themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT uwevolker themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT henriwallaschofski themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT matthiasschwab themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT matthiasschwab themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT matthiasschwab themembranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT annetnies membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT annetnies membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT stefanweiss membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT stefanweiss membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT elkeschaeffeler membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT elkeschaeffeler membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT ankehannemann membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT ankehannemann membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT uwevolker membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT uwevolker membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT henriwallaschofski membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT matthiasschwab membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT matthiasschwab membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans AT matthiasschwab membranetransporteroat7slc22a9isnotasusceptibilityfactorforosteoporosisineuropeans |