TY - JOUR
T1 - Pharmacogenetics
T2 - Potential role in the treatment of diabetes and obesity
AU - Vella, Adrian
AU - Camilleri, Michael
N1 - Funding Information:
Adrian Vella receives grant support from Amylin/Lilly and Merck. The authors acknowledge the support of the Mayo Clinic General Clinical Research Center supported by NIH grant RR024150. A Vella is supported by NIH grant DK078646 and M Camilleri is supported by grants DK02638, DK67071 and NIH P01-DK068055.
PY - 2008/5
Y1 - 2008/5
N2 - Background: Common genetic variation is associated with increased risk of common metabolic diseases such as type 1 and type 2 diabetes, and obesity. Increasing experience with genetic association studies has led to an understanding of the large sample sizes required to detect a weak to moderate genetic predisposition to disease, the need to reproduce such associations in independent cohorts, and the statistical criteria required to detect a true association. This approach has been used successfully to identify disease-associated gene variation usually in representative populations of large numbers. Objective: To review the current understanding of how common genetic variation influences predisposition to, and treatment of, metabolic disease. Methodology: Review of scientific literature. Results: While there has been progress in understanding how genetic variation predisposes to diabetes and obesity, and how candidate genes may alter drug response, several caveats limit the interpretation and significance of pharmacogenetic studies published to date: those caveats typically include relatively small numbers of participants and choice of endpoints in determining gene-associated differences in response, which may not be clinically significant or relevant as a biomarker or predictor of a desired clinical effect. The genetic variants studied at a given locus are often limited in number and may not represent a comprehensive map of the region under study. Conclusions: The pharmacogenetic associations in diabetes and obesity that have been reported to date have had limited impact on the choice of individual treatments. We perceive, however, that this field is in its infancy in these multifactorial metabolic diseases, and with further advances and future drug intervention trials designed in a way that allows a more clear interpretation of the impact of genetic variation on differences in drug response in obesity and diabetes, it is anticipated that pharmacogenetics will have a significant impact on individualizing medical care.
AB - Background: Common genetic variation is associated with increased risk of common metabolic diseases such as type 1 and type 2 diabetes, and obesity. Increasing experience with genetic association studies has led to an understanding of the large sample sizes required to detect a weak to moderate genetic predisposition to disease, the need to reproduce such associations in independent cohorts, and the statistical criteria required to detect a true association. This approach has been used successfully to identify disease-associated gene variation usually in representative populations of large numbers. Objective: To review the current understanding of how common genetic variation influences predisposition to, and treatment of, metabolic disease. Methodology: Review of scientific literature. Results: While there has been progress in understanding how genetic variation predisposes to diabetes and obesity, and how candidate genes may alter drug response, several caveats limit the interpretation and significance of pharmacogenetic studies published to date: those caveats typically include relatively small numbers of participants and choice of endpoints in determining gene-associated differences in response, which may not be clinically significant or relevant as a biomarker or predictor of a desired clinical effect. The genetic variants studied at a given locus are often limited in number and may not represent a comprehensive map of the region under study. Conclusions: The pharmacogenetic associations in diabetes and obesity that have been reported to date have had limited impact on the choice of individual treatments. We perceive, however, that this field is in its infancy in these multifactorial metabolic diseases, and with further advances and future drug intervention trials designed in a way that allows a more clear interpretation of the impact of genetic variation on differences in drug response in obesity and diabetes, it is anticipated that pharmacogenetics will have a significant impact on individualizing medical care.
KW - Common genetic variation
KW - Glucagon-like peptide-1
KW - Obesity
KW - Pharmacogenetics
KW - Sulfonylureas
KW - Thiazolidinediones
KW - Type 1 diabetes
KW - Type 2 diabetes
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U2 - 10.1517/14656566.9.7.1109
DO - 10.1517/14656566.9.7.1109
M3 - Review article
C2 - 18422469
AN - SCOPUS:43049170254
SN - 1465-6566
VL - 9
SP - 1109
EP - 1119
JO - Expert Opinion on Pharmacotherapy
JF - Expert Opinion on Pharmacotherapy
IS - 7
ER -