Genetic Variation among Pharmacogenes in the Sardinian Population

Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step f...
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Autor*in:	Maria Laura Idda [verfasserIn] Magdalena Zoledziewska [verfasserIn] Silvana Anna Maria Urru [verfasserIn] Gregory McInnes [verfasserIn] Alice Bilotta [verfasserIn] Viola Nuvoli [verfasserIn] Valeria Lodde [verfasserIn] Sandro Orrù [verfasserIn] David Schlessinger [verfasserIn] Francesco Cucca [verfasserIn] Matteo Floris [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	pharmacogenetics pharmacogenomics drug response

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 23(2022), 17, p 10058
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:17, p 10058

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms231710058

Katalog-ID:	DOAJ013266632

Internformat


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allfields	10.3390/ijms231710058 doi (DE-627)DOAJ013266632 (DE-599)DOAJ2fef4740a0a7463d994262e2afbc0d76 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Maria Laura Idda verfasserin aut Genetic Variation among Pharmacogenes in the Sardinian Population 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1577 unrelated sequenced Sardinians, an ancient island population that accounts for genetic variation in Europe as a whole, and, at the same time is enriched in genetic variants that are very rare elsewhere. To this end, we used PGxPOP, a PGx allele caller based on the guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), to identify the main phenotypes associated with the PGx alleles most represented in Sardinians. We estimated that 99.43% of Sardinian individuals might potentially respond atypically to at least one drug, that on average each individual is expected to have an abnormal response to about 17 drugs, and that for 27 drugs the fraction of the population at risk of atypical responses to therapy is more than 40%. Finally, we identified 174 pharmacogenetic variants for which the minor allele frequency was at least 10% higher among Sardinians as compared to other European populations, a fact that may contribute to substantial interpopulation variability in drug response phenotypes. This study provides baseline information for further large-scale pharmacogenomic investigations in the Sardinian population and underlines the importance of PGx characterization of diverse European populations, such as Sardinians. pharmacogenetics pharmacogenomics drug response Biology (General) Chemistry Magdalena Zoledziewska verfasserin aut Silvana Anna Maria Urru verfasserin aut Gregory McInnes verfasserin aut Alice Bilotta verfasserin aut Viola Nuvoli verfasserin aut Valeria Lodde verfasserin aut Sandro Orrù verfasserin aut David Schlessinger verfasserin aut Francesco Cucca verfasserin aut Matteo Floris verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 17, p 10058 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:17, p 10058 https://doi.org/10.3390/ijms231710058 kostenfrei https://doaj.org/article/2fef4740a0a7463d994262e2afbc0d76 kostenfrei https://www.mdpi.com/1422-0067/23/17/10058 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 17, p 10058
spelling	10.3390/ijms231710058 doi (DE-627)DOAJ013266632 (DE-599)DOAJ2fef4740a0a7463d994262e2afbc0d76 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Maria Laura Idda verfasserin aut Genetic Variation among Pharmacogenes in the Sardinian Population 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1577 unrelated sequenced Sardinians, an ancient island population that accounts for genetic variation in Europe as a whole, and, at the same time is enriched in genetic variants that are very rare elsewhere. To this end, we used PGxPOP, a PGx allele caller based on the guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), to identify the main phenotypes associated with the PGx alleles most represented in Sardinians. We estimated that 99.43% of Sardinian individuals might potentially respond atypically to at least one drug, that on average each individual is expected to have an abnormal response to about 17 drugs, and that for 27 drugs the fraction of the population at risk of atypical responses to therapy is more than 40%. Finally, we identified 174 pharmacogenetic variants for which the minor allele frequency was at least 10% higher among Sardinians as compared to other European populations, a fact that may contribute to substantial interpopulation variability in drug response phenotypes. This study provides baseline information for further large-scale pharmacogenomic investigations in the Sardinian population and underlines the importance of PGx characterization of diverse European populations, such as Sardinians. pharmacogenetics pharmacogenomics drug response Biology (General) Chemistry Magdalena Zoledziewska verfasserin aut Silvana Anna Maria Urru verfasserin aut Gregory McInnes verfasserin aut Alice Bilotta verfasserin aut Viola Nuvoli verfasserin aut Valeria Lodde verfasserin aut Sandro Orrù verfasserin aut David Schlessinger verfasserin aut Francesco Cucca verfasserin aut Matteo Floris verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 17, p 10058 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:17, p 10058 https://doi.org/10.3390/ijms231710058 kostenfrei https://doaj.org/article/2fef4740a0a7463d994262e2afbc0d76 kostenfrei https://www.mdpi.com/1422-0067/23/17/10058 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 17, p 10058
allfields_unstemmed	10.3390/ijms231710058 doi (DE-627)DOAJ013266632 (DE-599)DOAJ2fef4740a0a7463d994262e2afbc0d76 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Maria Laura Idda verfasserin aut Genetic Variation among Pharmacogenes in the Sardinian Population 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1577 unrelated sequenced Sardinians, an ancient island population that accounts for genetic variation in Europe as a whole, and, at the same time is enriched in genetic variants that are very rare elsewhere. To this end, we used PGxPOP, a PGx allele caller based on the guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), to identify the main phenotypes associated with the PGx alleles most represented in Sardinians. We estimated that 99.43% of Sardinian individuals might potentially respond atypically to at least one drug, that on average each individual is expected to have an abnormal response to about 17 drugs, and that for 27 drugs the fraction of the population at risk of atypical responses to therapy is more than 40%. Finally, we identified 174 pharmacogenetic variants for which the minor allele frequency was at least 10% higher among Sardinians as compared to other European populations, a fact that may contribute to substantial interpopulation variability in drug response phenotypes. This study provides baseline information for further large-scale pharmacogenomic investigations in the Sardinian population and underlines the importance of PGx characterization of diverse European populations, such as Sardinians. pharmacogenetics pharmacogenomics drug response Biology (General) Chemistry Magdalena Zoledziewska verfasserin aut Silvana Anna Maria Urru verfasserin aut Gregory McInnes verfasserin aut Alice Bilotta verfasserin aut Viola Nuvoli verfasserin aut Valeria Lodde verfasserin aut Sandro Orrù verfasserin aut David Schlessinger verfasserin aut Francesco Cucca verfasserin aut Matteo Floris verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 17, p 10058 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:17, p 10058 https://doi.org/10.3390/ijms231710058 kostenfrei https://doaj.org/article/2fef4740a0a7463d994262e2afbc0d76 kostenfrei https://www.mdpi.com/1422-0067/23/17/10058 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 17, p 10058
allfieldsGer	10.3390/ijms231710058 doi (DE-627)DOAJ013266632 (DE-599)DOAJ2fef4740a0a7463d994262e2afbc0d76 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Maria Laura Idda verfasserin aut Genetic Variation among Pharmacogenes in the Sardinian Population 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1577 unrelated sequenced Sardinians, an ancient island population that accounts for genetic variation in Europe as a whole, and, at the same time is enriched in genetic variants that are very rare elsewhere. To this end, we used PGxPOP, a PGx allele caller based on the guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), to identify the main phenotypes associated with the PGx alleles most represented in Sardinians. We estimated that 99.43% of Sardinian individuals might potentially respond atypically to at least one drug, that on average each individual is expected to have an abnormal response to about 17 drugs, and that for 27 drugs the fraction of the population at risk of atypical responses to therapy is more than 40%. Finally, we identified 174 pharmacogenetic variants for which the minor allele frequency was at least 10% higher among Sardinians as compared to other European populations, a fact that may contribute to substantial interpopulation variability in drug response phenotypes. This study provides baseline information for further large-scale pharmacogenomic investigations in the Sardinian population and underlines the importance of PGx characterization of diverse European populations, such as Sardinians. pharmacogenetics pharmacogenomics drug response Biology (General) Chemistry Magdalena Zoledziewska verfasserin aut Silvana Anna Maria Urru verfasserin aut Gregory McInnes verfasserin aut Alice Bilotta verfasserin aut Viola Nuvoli verfasserin aut Valeria Lodde verfasserin aut Sandro Orrù verfasserin aut David Schlessinger verfasserin aut Francesco Cucca verfasserin aut Matteo Floris verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 17, p 10058 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:17, p 10058 https://doi.org/10.3390/ijms231710058 kostenfrei https://doaj.org/article/2fef4740a0a7463d994262e2afbc0d76 kostenfrei https://www.mdpi.com/1422-0067/23/17/10058 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 17, p 10058
allfieldsSound	10.3390/ijms231710058 doi (DE-627)DOAJ013266632 (DE-599)DOAJ2fef4740a0a7463d994262e2afbc0d76 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Maria Laura Idda verfasserin aut Genetic Variation among Pharmacogenes in the Sardinian Population 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1577 unrelated sequenced Sardinians, an ancient island population that accounts for genetic variation in Europe as a whole, and, at the same time is enriched in genetic variants that are very rare elsewhere. To this end, we used PGxPOP, a PGx allele caller based on the guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), to identify the main phenotypes associated with the PGx alleles most represented in Sardinians. We estimated that 99.43% of Sardinian individuals might potentially respond atypically to at least one drug, that on average each individual is expected to have an abnormal response to about 17 drugs, and that for 27 drugs the fraction of the population at risk of atypical responses to therapy is more than 40%. Finally, we identified 174 pharmacogenetic variants for which the minor allele frequency was at least 10% higher among Sardinians as compared to other European populations, a fact that may contribute to substantial interpopulation variability in drug response phenotypes. This study provides baseline information for further large-scale pharmacogenomic investigations in the Sardinian population and underlines the importance of PGx characterization of diverse European populations, such as Sardinians. pharmacogenetics pharmacogenomics drug response Biology (General) Chemistry Magdalena Zoledziewska verfasserin aut Silvana Anna Maria Urru verfasserin aut Gregory McInnes verfasserin aut Alice Bilotta verfasserin aut Viola Nuvoli verfasserin aut Valeria Lodde verfasserin aut Sandro Orrù verfasserin aut David Schlessinger verfasserin aut Francesco Cucca verfasserin aut Matteo Floris verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 17, p 10058 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:17, p 10058 https://doi.org/10.3390/ijms231710058 kostenfrei https://doaj.org/article/2fef4740a0a7463d994262e2afbc0d76 kostenfrei https://www.mdpi.com/1422-0067/23/17/10058 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 17, p 10058
language	English
source	In International Journal of Molecular Sciences 23(2022), 17, p 10058 volume:23 year:2022 number:17, p 10058
sourceStr	In International Journal of Molecular Sciences 23(2022), 17, p 10058 volume:23 year:2022 number:17, p 10058
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	pharmacogenetics pharmacogenomics drug response Biology (General) Chemistry
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container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Maria Laura Idda @@aut@@ Magdalena Zoledziewska @@aut@@ Silvana Anna Maria Urru @@aut@@ Gregory McInnes @@aut@@ Alice Bilotta @@aut@@ Viola Nuvoli @@aut@@ Valeria Lodde @@aut@@ Sandro Orrù @@aut@@ David Schlessinger @@aut@@ Francesco Cucca @@aut@@ Matteo Floris @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	316340715
id	DOAJ013266632
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author	Maria Laura Idda
spellingShingle	Maria Laura Idda misc QH301-705.5 misc QD1-999 misc pharmacogenetics misc pharmacogenomics misc drug response misc Biology (General) misc Chemistry Genetic Variation among Pharmacogenes in the Sardinian Population
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topic_title	QH301-705.5 QD1-999 Genetic Variation among Pharmacogenes in the Sardinian Population pharmacogenetics pharmacogenomics drug response
topic	misc QH301-705.5 misc QD1-999 misc pharmacogenetics misc pharmacogenomics misc drug response misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc pharmacogenetics misc pharmacogenomics misc drug response misc Biology (General) misc Chemistry
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title	Genetic Variation among Pharmacogenes in the Sardinian Population
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title_full	Genetic Variation among Pharmacogenes in the Sardinian Population
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author_browse	Maria Laura Idda Magdalena Zoledziewska Silvana Anna Maria Urru Gregory McInnes Alice Bilotta Viola Nuvoli Valeria Lodde Sandro Orrù David Schlessinger Francesco Cucca Matteo Floris
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title_sort	genetic variation among pharmacogenes in the sardinian population
callnumber	QH301-705.5
title_auth	Genetic Variation among Pharmacogenes in the Sardinian Population
abstract	Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1577 unrelated sequenced Sardinians, an ancient island population that accounts for genetic variation in Europe as a whole, and, at the same time is enriched in genetic variants that are very rare elsewhere. To this end, we used PGxPOP, a PGx allele caller based on the guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), to identify the main phenotypes associated with the PGx alleles most represented in Sardinians. We estimated that 99.43% of Sardinian individuals might potentially respond atypically to at least one drug, that on average each individual is expected to have an abnormal response to about 17 drugs, and that for 27 drugs the fraction of the population at risk of atypical responses to therapy is more than 40%. Finally, we identified 174 pharmacogenetic variants for which the minor allele frequency was at least 10% higher among Sardinians as compared to other European populations, a fact that may contribute to substantial interpopulation variability in drug response phenotypes. This study provides baseline information for further large-scale pharmacogenomic investigations in the Sardinian population and underlines the importance of PGx characterization of diverse European populations, such as Sardinians.
abstractGer	Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1577 unrelated sequenced Sardinians, an ancient island population that accounts for genetic variation in Europe as a whole, and, at the same time is enriched in genetic variants that are very rare elsewhere. To this end, we used PGxPOP, a PGx allele caller based on the guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), to identify the main phenotypes associated with the PGx alleles most represented in Sardinians. We estimated that 99.43% of Sardinian individuals might potentially respond atypically to at least one drug, that on average each individual is expected to have an abnormal response to about 17 drugs, and that for 27 drugs the fraction of the population at risk of atypical responses to therapy is more than 40%. Finally, we identified 174 pharmacogenetic variants for which the minor allele frequency was at least 10% higher among Sardinians as compared to other European populations, a fact that may contribute to substantial interpopulation variability in drug response phenotypes. This study provides baseline information for further large-scale pharmacogenomic investigations in the Sardinian population and underlines the importance of PGx characterization of diverse European populations, such as Sardinians.
abstract_unstemmed	Pharmacogenetics (PGx) aims to identify the genetic factors that determine inter-individual differences in response to drug treatment maximizing efficacy while decreasing the risk of adverse events. Estimating the prevalence of PGx variants involved in drug response, is a critical preparatory step for large-scale implementation of a personalized medicine program in a target population. Here, we profiled pharmacogenetic variation in fourteen clinically relevant genes in a representative sample set of 1577 unrelated sequenced Sardinians, an ancient island population that accounts for genetic variation in Europe as a whole, and, at the same time is enriched in genetic variants that are very rare elsewhere. To this end, we used PGxPOP, a PGx allele caller based on the guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), to identify the main phenotypes associated with the PGx alleles most represented in Sardinians. We estimated that 99.43% of Sardinian individuals might potentially respond atypically to at least one drug, that on average each individual is expected to have an abnormal response to about 17 drugs, and that for 27 drugs the fraction of the population at risk of atypical responses to therapy is more than 40%. Finally, we identified 174 pharmacogenetic variants for which the minor allele frequency was at least 10% higher among Sardinians as compared to other European populations, a fact that may contribute to substantial interpopulation variability in drug response phenotypes. This study provides baseline information for further large-scale pharmacogenomic investigations in the Sardinian population and underlines the importance of PGx characterization of diverse European populations, such as Sardinians.
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title_short	Genetic Variation among Pharmacogenes in the Sardinian Population
url	https://doi.org/10.3390/ijms231710058 https://doaj.org/article/2fef4740a0a7463d994262e2afbc0d76 https://www.mdpi.com/1422-0067/23/17/10058 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067
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author2	Magdalena Zoledziewska Silvana Anna Maria Urru Gregory McInnes Alice Bilotta Viola Nuvoli Valeria Lodde Sandro Orrù David Schlessinger Francesco Cucca Matteo Floris
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