The APOA5-1131C allele may contribute to the increased susceptibility to diabetes mellitus in association with plasma triglyceride in Korean women

Abstract

[한글]

[영문]Background and objective: APOA5-1131C allele is associated with higher plasma triglyceride concentration and contributes to higher cardiovascular disease (CVD) risk in Koreans. Hypertriglyceridemia is not only a classical risk factor for CVD but also one of the commonly recognized lipid abnormalities in diabetes mellitus (DM), furthermore it is an independent risk factor for atherosclerosis in type 2 DM. Therefore, our study aimed to investigate the association of APOA5-1131T>C and the relative risk of DM in Korean, and their relationship with plasma lipid profile in Korean.Design and methods: Totally 3450 unrelated Korean women were included in this study [healthy control, n=2033; diabetes mellitus (DM), n=304, and metabolic abnormality (MA) (metabolic syndrome or impaired fasting glucose), n=1113]. Association of APOA5-1131T>C and DM risk were calculated by logistic regression analysis (odds ratio, OR; 95%confidence interval, CI) with adjustment for compounding factors. Differences in basic characteristics and biochemical parameters among groups were tested by one-way analysis of variance (ANOVA) followed by Bonferroni method with adjustment or notResults: The frequency of APOA5-1131C allele is higher in DM patients than non diabetic subjects. C carriers showed significantly higher risk of DM than TT genotype [OR0 1.39 (95% CI, 1.09?1.77), P=0.008] and the significance of the association still remained after the adjustment for age, BMI, menopause, smoking and drinking [OR1 1.61 (95% CI, 1.23-2.10), P<0.001]. Particularly, CC genotype showed a much higher increased risk of DM than TT genotype [OR0 1.93 (95% CI, 1.27-2.92), P=0.002, OR1 2.35 (95% CI, 1.46-3.77), P<0.001]. When adjusted for metabolic syndrome, C carriers still have a significantly high risk of DM [OR2 1.98 (95% CI, 1.09-3.59, p=0.024]. CC homozygote also showed high risk, but it turned to a tendency [OR2 2.51 (95% CI, 0.90-6.96, p=0.078]. Regarding lipid profiles, C carriers, particularly CC homozygote, had higher levels of TG, and lower levels of HDL-cholesterol in all three subjects groups. Apoplipoprotein A5 levels were also significantly associated with genotypes in healthy control and MA group, but not in DM patients. Fasting glucose levels were significantly positively correlated with plasma TG levels in whole or in each genotype of total population On the other hand, DM patients show the positive correlation in C carriers (r=0.165, p=0.035), which was much higher in CC genotype (r=0.395, p=0.021), but not in TT genotype (r=0.139, p=0.102). These patterns still retained after adjusted for age, BMI, menopause, smoking and drinking. In DM patients particularly with higher fasting glucose levels, CC homozygote showed a dramatically higher level of TG than TT genotype before and after the adjustment.Conclusion: Our new findings suggest that APOA5-1131C allele may contribute to the increased susceptibility of diabetes mellitus in association with plasma triglyceride in Korean women