Body fat percentage is a major determinant of total bilirubin independently of UGT1A1*28 polymorphism in young obese

Abstract

Objectives: Bilirubin has potential antioxidant and anti-inflammatory properties. The UGT1A1*28 polymorphism (TA repeats in the promoter region) is a major determinant of bilirubin levels and recent evidence suggests that raised adiposity may also be a contributing factor. We aimed to study the interaction between UGT1A1 polymorphism, hematological and anthropometric variables with total bilirubin levels in young individuals.

Methods: 350 obese (mean age of 11.6 years; 52% females) and 79 controls (mean age of 10.5 years; 59% females) were included. Total bilirubin and C-reactive protein (CRP) plasma levels, hemogram, anthropometric data and UGT1A1 polymorphism were determined. In a subgroup of 74 obese and 40 controls body composition was analyzed by dual-energy X-ray absorptiometry.

Results: The UGT1A1 genotype frequencies were 49.9%, 42.7% and 7.5% for 6/6, 6/7 and 7/7 genotypes, respectively. Patients with 7/7 genotype presented the highest total bilirubin levels, followed by 6/7 and 6/6 genotypes. Compared to controls, obese patients presented higher erythrocyte count, hematocrit, hemoglobin and CRP levels, but no differences in bilirubin or in UGT1A1 genotype distribution. Body fat percentage was inversely correlated with bilirubin in obese patients but not in controls. This inverse association was observed either in 6/7 or 6/6 genotype obese patients. UGT1A1 polymorphism and body fat percentage were the main factors affecting bilirubin levels within obese patients (linear regression analysis).

Conclusion: In obese children and adolescents, body fat composition and UGT1A1 polymorphism are independent determinants of total bilirubin levels. Obese individuals with 6/6 UGT1A1 genotype and higher body fat mass may benefit from a closer clinical follow-up.

Figure 1. Total bilirubin levels in all participants according to the number of TA repeats in the promoter region of UGT1A1 gene (A) and also according to group (B), control and obese.

The boxes represent the interquartile range (IQR), with the upper and lower edges of the boxes representing the 75th and 25th percentiles, respectively. The central horizontal lines within the boxes represent median levels for each group. The vertical whiskers above and below the boxes represent the range of outlying data points up to 1.5 times the IQR.

Figure 2. Total bilirubin (A) and C-reactive protein (B) levels in obese participants according to gender and to body fat percentage (n = 74), using the cut-off value of 42.5% (cut-off that corresponds to the median value for the obese group).

The boxes represent the interquartile range (IQR), with the upper and lower edges of the boxes representing the 75th and 25th percentiles, respectively. The central horizontal lines within the boxes represent median levels for each group. The vertical whiskers above and below the boxes represent the range of outlying data points up to 1.5 times the IQR.

Figure 3. Effect of body fat percentage on total bilirubin levels according to UGT1A1*28 polymorphism on obese patients.

For a better visualization of the results we used for body fat percentage a cut-off of 42.5% (cut-off that corresponds to the median value for the obese group). Results are presented as mean ± standard error of mean. The influence of body fat percentage, adjusted for UGT1A1 polymorphism, on total bilirubin levels, was highly significant (p = 0.009), by multiple regression analysis.