TY - JOUR
T1 - Association of UCP-3 rs1626521 with obesity and stomach functions in humans
AU - Acosta, Andres
AU - Camilleri, Michael
AU - Shin, Andrea
AU - Vazquez-Roque, Maria I.
AU - Iturrino, Johanna
AU - Lanza, Ian R.
AU - Nair, K. Sreekumaran
AU - Burton, Duane
AU - O'Neill, Jessica
AU - Eckert, Deborah
AU - Carlson, Paula
AU - Vella, Adrian
AU - Zinsmeister, Alan R.
N1 - Publisher Copyright:
© 2015 The Obesity Society.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Objective To examine the association of gene variants of uncoupling proteins (UCP)-2 and -3 with obesity and gastrointestinal (GI) traits. Methods In 255 overweight or obese adults, the associations of gene variants in UCP-2 (-3474, rs659366) and UCP-3 (rs1626521, rs2075577, rs15763) with body weight (BW) and GI traits were studied. Gene variants were genotyped by TaqMan® assay. The associations of genotypes with BW and GI traits (gastric emptying, gastric volume, satiety by buffet meal, satiation by nutrient drink test and GI hormones) were assessed using ANOVA corrected for false detection rate (FDR). Results A novel UCP-3 gene variant, rs1626521, was identified; it was associated with BW (P = 0.039), waist circumference (P = 0.035), and significantly higher postprandial gastric volume (P = 0.003) and calories ingested at buffet meal (P = 0.006, both significant with FDR). In a subgroup of 11 participants, rs1626521 was also associated with reduced mitochondrial bioenergetics efficiency in skeletal muscle (P = 0.051). In an in vitro study in HEK293 cells, rs1626521 reduced UCP-3 protein expression (P = 0.049). Associations detected between other genotypes and GI traits were nonsignificant with FDR. Conclusions A newly identified functional variant (rs1626521) in UCP-3 affects postprandial gastric functions and satiety and may contribute to weight gain and alter human mitochondrial function.
AB - Objective To examine the association of gene variants of uncoupling proteins (UCP)-2 and -3 with obesity and gastrointestinal (GI) traits. Methods In 255 overweight or obese adults, the associations of gene variants in UCP-2 (-3474, rs659366) and UCP-3 (rs1626521, rs2075577, rs15763) with body weight (BW) and GI traits were studied. Gene variants were genotyped by TaqMan® assay. The associations of genotypes with BW and GI traits (gastric emptying, gastric volume, satiety by buffet meal, satiation by nutrient drink test and GI hormones) were assessed using ANOVA corrected for false detection rate (FDR). Results A novel UCP-3 gene variant, rs1626521, was identified; it was associated with BW (P = 0.039), waist circumference (P = 0.035), and significantly higher postprandial gastric volume (P = 0.003) and calories ingested at buffet meal (P = 0.006, both significant with FDR). In a subgroup of 11 participants, rs1626521 was also associated with reduced mitochondrial bioenergetics efficiency in skeletal muscle (P = 0.051). In an in vitro study in HEK293 cells, rs1626521 reduced UCP-3 protein expression (P = 0.049). Associations detected between other genotypes and GI traits were nonsignificant with FDR. Conclusions A newly identified functional variant (rs1626521) in UCP-3 affects postprandial gastric functions and satiety and may contribute to weight gain and alter human mitochondrial function.
UR - http://www.scopus.com/inward/record.url?scp=84925858696&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925858696&partnerID=8YFLogxK
U2 - 10.1002/oby.21039
DO - 10.1002/oby.21039
M3 - Article
C2 - 25755013
AN - SCOPUS:84925858696
SN - 1930-7381
VL - 23
SP - 898
EP - 906
JO - Obesity
JF - Obesity
IS - 4
ER -