The UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms are associated with premature coronary artery disease and cardiovascular risk factors in Mexican population

Abstract

We examined the role of UCP gene polymorphisms as susceptibility markers for premature coronary artery disease (pCAD). The UCP2 Ala55Val (C/T rs660339), UCP2 -866G/A (rs659366), and UCP3 -55C/T (rs1800849) polymorphisms were genotyped in 948 patients with pCAD, and 763 controls. The distribution of the UCP2 A55V (C/T rs660339) and UCP3 -55 (rs1800849) was similar in patients and controls. However, under a recessive model, the UCP2 -866 (rs659366) A allele was associated with increased risk of developing pCAD (OR = 1.43, Pc = 0.003). On the other hand, patients with pCAD and UCP2 A55V (rs660339) TT showed high levels of visceral abdominal fat (VAF) (Pc = 0.002), low levels of subcutaneous abdominal fat (SAF) (Pc = 0.001) and high VAT/SAT ratio (Pc < 0.001). Also, patients with UCP2 -866 (rs659366) AA showed increased levels of VAF (Pc = 0.003), low levels of SAF (Pc = 0.001) and a high VAT/SAT ratio (Pc = 0.002), whereas patients with the UCP3 -55 (rs1800849) TT presented high levels of VAF (Pc = 0.002). The results suggest the association of the UCP2 -866 (rs659366) polymorphism with risk of developing pCAD. Some polymorphisms were associated with abdominal fat levels and cardiovascular risk factors.

Association of uncoupling protein (Ucp) gene polymorphisms with cardiometabolic diseases

“…AA genotype carriers who survived ischemic stroke showed a higher functional status as compared with GG and GA genotype carriers (Díaz-Maroto Cicuéndez et al 2017). At the same time, the A allele increased the risk of developing coronary artery disease in the Mexican population (Gamboa et al 2018) and in males of the European population (Dhamrait et al 2004). The Ala55Val polymorphism is in Ucp2 exon 4, where a C/ T nucleotide substitution leads to a substitution of alanine for valine at position 55 of the UCP2 amino acid sequence (Fig.…”

Variability in oxidative stress-related genes (SOD2, CAT, GPX1, GSTP1, NOS3, NFE2L2, and UCP2) and susceptibility to migraine clinical phenotypes and features

“…One of the most reported UCP2 variant is the missense variant rs660339 in exon 4, a C to T transition, resulting in an amino acid substitution at position 55 of the UCP2 (Ala55Val) which seems to modify the uncoupling degree and consequently protein activity ( 72 ). In particular, the Val/Val genotype has been associated with lower degree of uncoupling, increased metabolic efficiency, lesser fat oxidation, reduced energy expenditure, higher exercise efficiency, higher risk of obesity and diabetes, elevated atherogenic index, and greater weight loss compared to the Ala/Val and Ala/Ala genotypes ( 77 , 78 ). UCP2 demonstrates tissue specific physiological effects as suggested by its tissue-specific regulation e.g., in the brain UCP2 functions as a regulator of oxidative stress.…”

Association and interaction effect of UCP2 gene polymorphisms and dietary factors with congenital heart diseases in Chinese Han population

“…However, some evidence has suggested that the mutations of UCP2 genes can affect the activity or expression levels of UCP2 by increasing the coupling of oxidative phosphorylation, which might cause the reduction of energy expenditure and subsequently contribute to the development of obesity and diabetes 14 . At present, most previous studies have found that two common polymorphisms of UCP2 gene including rs659366 (located in the promoter region) and rs660339 (a missense variant in exon 4) were closely associated with obesity and diabetes 12 , 31 , 32 . Furthermore, maternal obesity and diabetes have been identified as risk factors of CHDs, which indirectly indicated that genetic variants of UCP2 may be associated with the risk of CHDs in offspring.…”