Association of UCP‐3 rs1626521 with obesity and stomach functions in humans

Abstract

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, we studied the associations of gene variants in UCP-2 (−3474, rs659366) and UCP-3 (rs1626521, rs2075577, rs15763) with body weight (BW) and GI traits. Gene variants were genotyped by TaqMan® assay. We assessed 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) using ANCOVA, corrected for false detection rate (FDR). Results We identified a novel UCP-3 gene variant, rs1626521; it was associated with BW (p=0.039), waist circumference (p=0.035), and with 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 non-significant 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.

Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians

“…However, other studies show no effect of sod2 - on murine life span (Gallagher et al 2000; Zhang et al 2009). According to our current study, the minor alleles of the UCP2/3 SNPs examined were correlated with increased gene expression, which is evident from the gene reporter assay with the UCP3 SNP (Acosta et al 2015). Because increased expression of UCP2/3 corresponds to increased uncoupling, and increased uncoupling is expected to reduce ROS production, the minor alleles should be associated with healthier aging.…”

“…SNP rs1626521, located in the 3′ untranslated region of UCP3 (Fig. 4), is associated with body weight and mitochondrial energy metabolism and affects expression of a reporter gene in an allele-specific manner (Acosta et al 2015). Therefore, we chose these three SNPs (Table 1) to test for association with FI 34 .…”

“…The UCP3 SNP rs1626521 is functional and associated with body weight and mitochondrial energy metabolism in skeletal muscle (Acosta et al 2015). Other SNPs in UCP3 are associated with childhood obesity and hand-grip strength (Crocco et al 2011; Dato et al 2012; Musa et al 2012).…”

“…4), increasing the likelihood of the functionality of the SNP. Expression of a reporter gene in the presence of the minor allele is significantly higher than in the presence of the major allele (Acosta et al 2015). The interaction of the SNP with RMR indicates that the positive association of RMR with FI 34 depends on the minor allele of the SNP (Fig.…”

“…The population study of rs1626521 by Acosta et al (2015) involved both males and females, but mostly in their 30s. In our study, the largest gender difference was in FFM.…”