Synergistic effects of genetic variants of APOA5 and BTN2A1 on dyslipidemia or metabolic syndrome

Abstract

Abstract. We previously showed that the -1131T→C polymorphism (rs662799) of the apolipoprotein A-V gene (APOA5) and the C→T polymorphism (rs6929846) of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) were significantly associated with an increased serum concentration of triglycerides, a decreased serum concentration of high density lipoprotein (HDL)-cholesterol, and the prevalence of metabolic syndrome (MetS) in Japanese individuals. The purpose of the present study was to examine whether these polymorphisms synergistically affect the prevalence of dyslipidemia and MetS in East Asian populations. The study populations comprised 7471 Japanese and 3529 Korean individuals in the dyslipidemia study, and 3474 Japanese and 1671 Korean individuals in the MetS study. Multivariable logistic regression analysis of combined genotypes with adjustment for age, gender and diabetes mellitus revealed that rs662799 and rs6929846 significantly and synergistically affected dyslipidemia. Japanese or Korean individuals with the C allele of APOA5 and the T allele of BTN2A1 had a 2.05-or 1.92-fold increased risk for hypertriglyceridemia and a 1.82-or 1.56-fold increased risk for hypo-HDL-cholesterolemia, respectively, compared to those with the TT genotype of APOA5 and the CC genotype of BTN2A1. Similar analysis with adjustment for age and gender revealed that Japanese individuals, but not Korean individuals, with the C allele of APOA5 and the T allele of BTN2A1 had a 2.87-fold increased risk for MetS compared to those with the TT genotype of APOA5 and the CC genotype of BTN2A1. Genetic variants of APOA5 and BTN2A1 may synergistically affect the prevalence of dyslipidemia in East Asian populations and of MetS in Japanese individuals.

Association and interaction of APOA5, BUD13, CETP, LIPA and health-related behavior with metabolic syndrome in a Taiwanese population

“…In accordance with our analysis, Wu et al reported that APOA5 rs662799 had a positive interaction with environmental factors, such as tobacco use and alcohol consumption, on MetS with participations in China32. Likewise, a previous study by Hiramatsu et al found the synergistic effects of APOA5 rs662799 and the rs6929846 SNP of the butyrophilin subfamily 2 member A1 ( BTN2A1 ) gene on the development of MetS in Japanese individuals33. Son et al also suggested an interaction between APOA5 rs662799 and alcohol drinking as well as an interaction between APOA5 rs662799 and physical activity in affecting triglyceride levels in Korean men, but no interaction between APOA5 rs662799 and smoking status34.…”

Haplotype analysis of the Apolipoprotein A5 gene in Moroccan patients with the metabolic syndrome

“…Analysis of constructed haplotypes with SNPs in MTHFR, APOA5 and APOC3 genes, showed a highly significant association between one haplotype and MS in the Greek Population [ 43 ]. Gene-gene interaction suggested that polymorphisms in APOA5 and BTN2A1 genes may have synergistic effects on the development of MS in Japanese individuals [ 44 ].…”

Recent Advances in Kawasaki Disease

“… 31 This might be from synergistic effects of genetic variants of ITPKC and CASP3 , which could be observed in other diseases. 32 33 Based on these results, administration of cyclosporine A for the treatment of IVIG-resistant KD patients is theoretically feasible, because cyclosporine A suppresses activation of NFAT. Currently, cyclosporine A is already being used 34 in treatment and further research projects are ongoing.…”