The FOXO3A rs2802292 G-Allele Associates with Improved Peripheral and Hepatic Insulin Sensitivity and Increased Skeletal Muscle-FOXO3A mRNA Expression in Twins
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The FOXO3A rs2802292 G-Allele Associates with Improved Peripheral and Hepatic Insulin Sensitivity and Increased Skeletal Muscle-FOXO3A mRNA Expression in Twins. / Banasik, Karina; Ribel-Madsen, Rasmus; Gjesing, Anette P; Wegner, Lise; Andersson, Åsa; Poulsen, Pernille; Borglykke, Anders; Witte, Daniel R; Pedersen, Oluf; Hansen, Torben; Vaag, Allan.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 1, 01.01.2011, p. E119-24.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The FOXO3A rs2802292 G-Allele Associates with Improved Peripheral and Hepatic Insulin Sensitivity and Increased Skeletal Muscle-FOXO3A mRNA Expression in Twins
AU - Banasik, Karina
AU - Ribel-Madsen, Rasmus
AU - Gjesing, Anette P
AU - Wegner, Lise
AU - Andersson, Åsa
AU - Poulsen, Pernille
AU - Borglykke, Anders
AU - Witte, Daniel R
AU - Pedersen, Oluf
AU - Hansen, Torben
AU - Vaag, Allan
PY - 2011/1/1
Y1 - 2011/1/1
N2 - Objective: The minor G-allele of FOXO3A rs2802292 has been associated with longevity. We aimed to investigate whether a phenotype related to healthy metabolic aging could be identified in individuals carrying the longevity-associated FOXO3A rs2802292 G-allele. Research Design and Methods: rs2802292 was genotyped in a phenotypically well-characterized population of young and elderly twins (n = 190) and in the population-based Inter99 cohort (n = 5768). All participants underwent oral glucose tolerance tests, and the twin population was additionally examined with an iv glucose tolerance test and a hyperinsulinemic, euglycemic clamp. Basal and insulin-stimulated FOXO3A mRNA expression was assessed in skeletal muscle biopsies from the twin population. Results: In the twin sample, carriers of the minor G-allele of rs2802292 showed reduced fasting plasma insulin [per allele effect (ß) = -13% (-24; -1) (95% confidence interval), P = 0.03] and lower incremental area under the curve 0–120 min for insulin after an oral glucose load [ß = -14% (-23; -5), P = 0.005]. The G-allele was associated with increased peripheral insulin action [glucose disposal rate clamp, ß = 0.85 mg · kgfat-free mass-1 · min-1 (0.049; 1.64), P = 0.04] and lower hepatic insulin resistance index [ß = -13% (-25; -1), P = 0.03]. Furthermore, carriers of the G-allele had increased basal FOXO3A mRNA expression in skeletal muscle compared with T-allele carriers [ß = 16% (0; 33), P = 0.047]. In the Inter99 sample, we found an association with reduced incremental area under the curve 0–120 min for insulin after an oral glucose load [ß = -3% (-5; -0.07), P = 0.04], but this association was not significant after adjustment for body mass index. Conclusion: Our data indicate that the minor G-allele of FOXO3A rs2802292 is associated with enhanced peripheral and hepatic insulin sensitivity in our small twin cohort, which may be mediated through increased FOXO3A mRNA expression, although no major metabolic impact of rs2802292 was found in the large Inter99 cohort.
AB - Objective: The minor G-allele of FOXO3A rs2802292 has been associated with longevity. We aimed to investigate whether a phenotype related to healthy metabolic aging could be identified in individuals carrying the longevity-associated FOXO3A rs2802292 G-allele. Research Design and Methods: rs2802292 was genotyped in a phenotypically well-characterized population of young and elderly twins (n = 190) and in the population-based Inter99 cohort (n = 5768). All participants underwent oral glucose tolerance tests, and the twin population was additionally examined with an iv glucose tolerance test and a hyperinsulinemic, euglycemic clamp. Basal and insulin-stimulated FOXO3A mRNA expression was assessed in skeletal muscle biopsies from the twin population. Results: In the twin sample, carriers of the minor G-allele of rs2802292 showed reduced fasting plasma insulin [per allele effect (ß) = -13% (-24; -1) (95% confidence interval), P = 0.03] and lower incremental area under the curve 0–120 min for insulin after an oral glucose load [ß = -14% (-23; -5), P = 0.005]. The G-allele was associated with increased peripheral insulin action [glucose disposal rate clamp, ß = 0.85 mg · kgfat-free mass-1 · min-1 (0.049; 1.64), P = 0.04] and lower hepatic insulin resistance index [ß = -13% (-25; -1), P = 0.03]. Furthermore, carriers of the G-allele had increased basal FOXO3A mRNA expression in skeletal muscle compared with T-allele carriers [ß = 16% (0; 33), P = 0.047]. In the Inter99 sample, we found an association with reduced incremental area under the curve 0–120 min for insulin after an oral glucose load [ß = -3% (-5; -0.07), P = 0.04], but this association was not significant after adjustment for body mass index. Conclusion: Our data indicate that the minor G-allele of FOXO3A rs2802292 is associated with enhanced peripheral and hepatic insulin sensitivity in our small twin cohort, which may be mediated through increased FOXO3A mRNA expression, although no major metabolic impact of rs2802292 was found in the large Inter99 cohort.
KW - Absorptiometry, Photon
KW - Adult
KW - Aged
KW - Alleles
KW - Area Under Curve
KW - Blood Glucose
KW - Body Composition
KW - Female
KW - Forkhead Transcription Factors
KW - Genotype
KW - Glucose Clamp Technique
KW - Glucose Tolerance Test
KW - Humans
KW - Insulin
KW - Insulin Resistance
KW - Liver
KW - Male
KW - Middle Aged
KW - Muscle, Skeletal
KW - RNA, Messenger
KW - Twins
U2 - 10.1210/jc.2010-0881
DO - 10.1210/jc.2010-0881
M3 - Journal article
C2 - 20881262
VL - 96
SP - E119-24
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 1
ER -
ID: 38335126