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Association between mu-opioid receptor-1 102T>C polymorphism and intermediate type 2 diabetes phenotypes: results from the Quebec Family Study (QFS).
Clin Exp Pharmacol Physiol. 2008 Sep; 35(9):1018-22.CE

Abstract

It has been suggested recently that molecules expressed both in the pancreas and hypothalamus, such as mu-opioid receptor 1 (OPRM1), could form an integrated brain-liver system, which may sense glucose levels and therefore contribute to the development of type 2 diabetes mellitus (T2DM). In the present study, we tested associations between OPRM1 gene polymorphisms (rs1799971, 102T/C and rs0648007G/A) and indices of glucose tolerance, insulin sensitivity (IS) and insulin secretion derived from plasma measures obtained in a fasting state and following a 75 g oral glucose tolerance test (OGTT) in 749 subjects from the Quebec Family Study (QFS). Polymorphisms were tested for association with glucose tolerance (normal vs IFG and T2DM combined) by calculating a chi(2) statistic and corresponding P values, whereas associations with quantitative measures of glucose tolerance, IS and insulin secretion were tested using mixed linear models implemented in the MIXED procedure of sas (SAS Institute, Cary, NC, USA). Associations were found between 102T/C OPRM1 and indices of glucose tolerance and IS. Compared with T/T homozygotes, carriers of the OPRM1 C-102 variant exhibited a better glucose tolerance with a lower (P = 0.006) glucose area under the curve (AUC) following the OGTT and a better IS with a higher (P = 0.03) value of the Cederholm index, a numerical index of the curve relating glucose uptake to the log(10) plasma insulin levels during the OGTT. The results of the present study reveal that the 102T/C OPRM1 gene polymorphism is associated with a better glucose tolerance and improved IS, both of which suggest a potential protective effect of this variant on T2DM risk.

Authors+Show Affiliations

Department of Preventive Medicine, Division of Kinesiology, Laval University, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18518884

Citation

Ruchat, Stephanie-May, et al. "Association Between Mu-opioid Receptor-1 102T>C Polymorphism and Intermediate Type 2 Diabetes Phenotypes: Results From the Quebec Family Study (QFS)." Clinical and Experimental Pharmacology & Physiology, vol. 35, no. 9, 2008, pp. 1018-22.
Ruchat SM, Girard M, Weisnagel SJ, et al. Association between mu-opioid receptor-1 102T>C polymorphism and intermediate type 2 diabetes phenotypes: results from the Quebec Family Study (QFS). Clin Exp Pharmacol Physiol. 2008;35(9):1018-22.
Ruchat, S. M., Girard, M., Weisnagel, S. J., Bouchard, C., Vohl, M. C., & Pérusse, L. (2008). Association between mu-opioid receptor-1 102T>C polymorphism and intermediate type 2 diabetes phenotypes: results from the Quebec Family Study (QFS). Clinical and Experimental Pharmacology & Physiology, 35(9), 1018-22. https://doi.org/10.1111/j.1440-1681.2008.04972.x
Ruchat SM, et al. Association Between Mu-opioid Receptor-1 102T>C Polymorphism and Intermediate Type 2 Diabetes Phenotypes: Results From the Quebec Family Study (QFS). Clin Exp Pharmacol Physiol. 2008;35(9):1018-22. PubMed PMID: 18518884.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association between mu-opioid receptor-1 102T>C polymorphism and intermediate type 2 diabetes phenotypes: results from the Quebec Family Study (QFS). AU - Ruchat,Stephanie-May, AU - Girard,Martine, AU - Weisnagel,S John, AU - Bouchard,Claude, AU - Vohl,Marie-Claude, AU - Pérusse,Louis, Y1 - 2008/06/01/ PY - 2008/6/4/pubmed PY - 2009/1/17/medline PY - 2008/6/4/entrez SP - 1018 EP - 22 JF - Clinical and experimental pharmacology & physiology JO - Clin. Exp. Pharmacol. Physiol. VL - 35 IS - 9 N2 - It has been suggested recently that molecules expressed both in the pancreas and hypothalamus, such as mu-opioid receptor 1 (OPRM1), could form an integrated brain-liver system, which may sense glucose levels and therefore contribute to the development of type 2 diabetes mellitus (T2DM). In the present study, we tested associations between OPRM1 gene polymorphisms (rs1799971, 102T/C and rs0648007G/A) and indices of glucose tolerance, insulin sensitivity (IS) and insulin secretion derived from plasma measures obtained in a fasting state and following a 75 g oral glucose tolerance test (OGTT) in 749 subjects from the Quebec Family Study (QFS). Polymorphisms were tested for association with glucose tolerance (normal vs IFG and T2DM combined) by calculating a chi(2) statistic and corresponding P values, whereas associations with quantitative measures of glucose tolerance, IS and insulin secretion were tested using mixed linear models implemented in the MIXED procedure of sas (SAS Institute, Cary, NC, USA). Associations were found between 102T/C OPRM1 and indices of glucose tolerance and IS. Compared with T/T homozygotes, carriers of the OPRM1 C-102 variant exhibited a better glucose tolerance with a lower (P = 0.006) glucose area under the curve (AUC) following the OGTT and a better IS with a higher (P = 0.03) value of the Cederholm index, a numerical index of the curve relating glucose uptake to the log(10) plasma insulin levels during the OGTT. The results of the present study reveal that the 102T/C OPRM1 gene polymorphism is associated with a better glucose tolerance and improved IS, both of which suggest a potential protective effect of this variant on T2DM risk. SN - 1440-1681 UR - https://www.unboundmedicine.com/medline/citation/18518884/Association_between_mu_opioid_receptor_1_102T>C_polymorphism_and_intermediate_type_2_diabetes_phenotypes:_results_from_the_Quebec_Family_Study__QFS__ L2 - https://doi.org/10.1111/j.1440-1681.2008.04972.x DB - PRIME DP - Unbound Medicine ER -