Central obesity in males affected by a dyslipidemia-associated genetic polymorphism on APOA1/C3/A4/A5 gene cluster

Abstract

Background: Central obesity is a rising epidemic, and often occurs in parallel with dyslipidemia. Furthermore, enhancement of ectopic fat deposition has been observed in both human studies and animal models of altered lipidemic control. Though APOA1/C3/A4/A5 genetic polymorphisms are associated with dyslipidemia, their effect on central obesity is less known.

Method: The anthropometric and metabolic parameters were taken from obese (body mass index (BMI) 25 kg m(-2)) and non-obese healthy (BMI <25) Taiwanese patients at the initiation weight-loss intervention and 6 months later. The effects of APOA1/C3/A4/A5 genetic polymorphisms were analyzed cross-sectionally and longitudinally. Gender contributions were specifically examined.

Patients: Three hundred and ninety-eight participants (obese n=262; non-obese healthy n=136) were recruited in total, and 130 obese patients underwent weight-loss treatments.

Results: APOA5 rs662799 minor allele carriage was associated with unfavorable metabolic profiles in obese but not non-obese individuals at baseline. Further analysis identified gender-genotype interactions in waist-hip ratio (WHR), and that one rs662799 minor allele increased 0.032 WHR unit in obese males as analyzed by linear regression adjusted for age, BMI and plasma triglyceride (TG) (95% confidence interval (CI)=0.014-0.050, P=0.001). The rs662799-associated WHR elevation resulted in increased frequency of central obesity (WHR 1.0) in rs662799 carrying obese males as analyzed by binary logistic regression adjusted for age, BMI and plasma TG (odds ratio=6.52, 95% CI=1.87-22.73, P=0.003). In contrast, APOA5 rs662799 and central obesity were no longer correlated 6 months into weight-loss treatments, owing to significant WHR reductions in male rs662799 minor allele carriers (P=0.001). Meanwhile, hypertriglyceridemia was more prevalent in both male and female obese rs662799 minor allele carriers at baseline (males, P=0.034, females, P=0.007).

Conclusion: This study highlights the gender-specific and weight-sensitive effects of APOA5 rs662799 on central obesity in Taiwanese individuals, and that these effects are dyslipidemia-independent and weight-loss responsive.

Figure 1

Test of gender- APOA5 rs662799 genotype interaction in WHR, plasma TG, BMI and plasma HDL-C in obese patients. The mean±s.d. values of analyzed parameter (WHR (a), TG (b), BMI (c) and HDL-c (d)) are shown under the designated APOA5 rs662799 genotype in a gender-specific manner. The cutoff values for elevated WHR (⩾1.0 unit for males and ⩾0.9 unit for females), hyper-TG (TG ⩾1.7 mmol l⁻¹), low HDL-C (HDL-C <1.0 mmol^−l for males and <1.3 mmol^−l for females) are shown as dashed line in figures. The number of individuals with the anthropometric and metabolic conditions is shown under the designated groups. The differences in mean±s.d. values were tested by one-way analysis of variance (ANOVA). The genotype–gender interactions were tested by general linear model univariate analysis.

Figure 2

Obese males carrying APOA5 rs662799 C allele have significant improvements in BMI, WHR and TG at 6 months after weight-loss intervention. The improvements in BMI (a), WHR (b) and TG (c) are shown. The values shown under specified timepoints or above genotype subgroups were mean±s.d. Paired t-test was used for comparing 0 month and 6 months values in specified subgroups, while the Student's t-test was used for comparing values between different groups.