Risk Factors Related to Resting Metabolic Rate-Related DNAJC6 Gene Variation in Children with Overweight/Obesity: 3-Year Panel Study

Abstract

This study investigated how the DNACJ6 gene variation related to RMR alteration affects risk factors of obese environments in children with obesity aged 8-9.

Methods: Over a three-year follow-up period, 63.3% of original students participated. Changes in the variables (anthropometrics, blood biochemistry, and dietary intakes) were analyzed and compared between those without obesity (non-OB) and with obesity (OB) classified at the study endpoint.

Result: The average MAF of nine SNPs (D-1 to D-IX) was defined as 18.1%. The OB group showed greater increases in RMR, BMI, WC, and SBP, while the non-OB group had significantly greater increases in HDL and intakes of nutrients (e.g., total calories, vitamins B2, C, folate, A, retinol, iron, and zinc). Increased RMR, BMI, BW, and RMR/BW changes were observed with mutant allele of D-I SNP, which was also associated with a higher prevalence of obesity. Greater increases in animal fat intake, including saturated fatty acids and retinol, were noted in the minor alleles of D-VI, D-VII, D-VIII, and D-IX SNPs compared to those of the major alleles. The odds ratio for BMI risk was significantly higher in the mutant alleles of D-I (rs17127601), D-VII (rs1334880), and D-VIII (rs7354899) compared to the wild type, with increases of 2.59 times (CI; 1.068-6.274), 1.86 times (CI; 1.012-3.422), and 1.85 times (CI; 1.008-3.416), respectively. RMR was a mild risk factor in minors of the D-1, D-VII, and D-VIII; however, a higher RMR/BW ratio significantly correlated with decreased BMI risk, and this effect was found in only the major alleles of D-I, D-VII, and D-VIII SNPs, not in the minor alleles. High retinol intake appeared to reduce obesity risk in the minor alleles of the D-I, D-VII, and D-VIII SNPs, even though intake of animal fats and retinol remained higher among minors over the three years.

Conclusions: These findings suggest that the RMR/BW ratio and dietary fat/retinol intake should be considered in DNACJ6-gene-based precision medicine approaches for pediatric obesity prevention, particularly for boys.

Keywords: DNAJC6; children obesity; dietary fat; dietary retinol; energy expenditure; resting metabolic rate (RMR); three-year panel study.

Figure 1

Flowchart of the 3-year panel study accounting the subjects. (*; [7]).

Figure 2

The positive correlation between RMR and BMI (A) and the negative correlation between RMR/BW and BMI (B). The negative correlation between RMR/BW and BMI was more powerful than the positive correlation between RMR and BMI. The regression model for non-OB subjects (blue line) was significantly more explanatory than that of OB subjects (red line) in both A and B cases. The negative correlation between RMR and BMI in non-OB group (R² = 59.1%) was more powerful compared to OB group (R² = 37.82%).

Figure 3

The significant differences in changes in variables in major (wild) and minor (mutant) alleles of D-1 (rs17127601). (A) The changes in RMR, BMI, or BW were higher in minor than major allele of only rs17127601 SNP (Welch’s T-test), but the other minor alleles of 8 SNPs did not change RMR, BMI, and BW compared to majors. Significant differences in the changes in dietaty intakes between major and minor alleles of D-VI, D-VII, D-VIII, and D-IX SNPs. (B) Diet variables related to fat intake were risk variables in minor allele of D-VI (rs10789182), D-VII (rs1334880), D-VIII (rs7354899), and D-IX (rs1334881) SNPs. All dietary intakes were adjusted according to energy intake in 2009 and 2012, respectively. The ranges of SD values in major and minor were (17.89~18.07 and 22.81~22.92) for animal fat intake, (8.63~8.67 and 13.61~13.65) for SFA intake, and (153.35~153.73 and 196.80~197.15) for retinol intake.

Figure 4

Relative frequency of obesity (%) in the quartiles of RMR/BW changes of majors (A) and minors (B) in D-1, D-VII, and D-VIII SNPs. By the Cochran–Armitage test, the prevalence of obesity was significantly decreased (p-^trend < 0.05) by increasing the changes in RMR/BW for 3 years in major alleles only in all three SNPs, D-I, VII, and D-VIII, compared to minor alleles. In major alleles, the averages of quartile values (Q1~Q4) of RMR/BW changes for 3 years were Q1 (<4.3), Q2 (~5.2), Q3 (~7.19), and Q4 (>7.2) compared to the minor alleles (Q1, <4.3; Q2, ~5.3; Q3, ~7.49; and Q4, >7.5) (D-I (rs17127601), D-VII(rs1334880), and D-VIII (rs7354899)).