Gender-Based Differences on the Association between Salt-Sensitive Genes and Obesity in Korean Children Aged between 8 and 9 Years

<div><p>Background</p><p>High sodium intake is associated with the development of chronic diseases such as obesity. Although its role in obesity remains controversial, there may be a correlation between salt sensitivity and the early onset of chronic diseases in obese children.</p><p>Methods</p><p>In all, 2,163 Korean children (1,106 boys and 1,057 girls) aged 8–9 years were recruited from seven elementary schools in Seoul. To evaluate whether obesity risk was modulated by the salt sensitivity, 11 SNPs related to salt sensitive genes (SSG) became the target of sodium intakes in obese children.</p><p>Results</p><p>BP, HOMA-IR, LDLc, TG, and the girls’ sodium intake significantly increased, but HDLc significantly decreased with increase in BMI. Regardless of sex, the obesity risk was 5.27-fold (CI; 1.320–27.560) higher in the Q2 to Q5 of sodium intake adjusted by energy (4044.9–5058.9 mg/day) than in the lowest Q1 level (2287.6 mg/day) in obese children. BP was sensitively dependent on insulin resistance and lipid accumulation in all subjects; however, sodium intake may be an independent risk factor of obesity without increasing BP in girls. <i>GRK4 A486V</i> mutant homozygote was highly distributed in the obese group, but other SNPs had no impact. The obesity risk increased 7.06, 16.8, and 46.09-fold more in boys with <i>GRK4 A486V</i>, <i>ACE</i>, and <i>SLC12A3</i> mutants as sodium intake increased. Among girls, the obesity risk increased in <i>GRK4 A486V</i> heterozygote and <i>CYP11β-2</i> mutant homozygote although sodium intake was relatively lower, implying that <i>ACE</i>, <i>SLC12A</i>, <i>CYP11β-2</i>, and <i>GRK4 A486V</i> polymorphisms showed gender-based differences with regard to interaction between sodium intake and obesity.</p><p>Conclusion</p><p>A high sodium intake markedly increased the obesity risk in variants of <i>GRK4 A486V</i> regardless of sex. The obesity risk increased with <i>GRK4 A486V</i>, <i>ACE</i>, and <i>SLC12A3</i> variants in boys, whereas it increased with <i>GRK4 A486V</i> and <i>CYP11B2</i> variants in girls as sodium intake increased. Obese children with the specific gene variants are recommended to reduce their sodium intake.</p></div

Odds ratio (OR) and 95% confidence interval (CI) for obesity risk by quintiles (Q1-Q5) of sodium intake with energy adjustment (residual-Na) were estimated in total children.

<p>The dietary sodium intakes increases, the risk of obesity significantly increases in obesity group (black bar; P-<i>trend</i> < 0.05), not in overweight group (gray bar). This figure was shown by comparison with the 1^st quintile vs all the others combined. Multivariate logistic regression models after adjustment for age, sex, mother’s BMI, father’s BMI, and education levels (<10 years, 10~12, 13~16 years, and >16 years) of the mother and father, dietary fat, systolic blood pressure and regular physical activity (no, yes). Means of residual-Na in each quintile for total subjects are 2287.6, 2998.9, 3496.8, 4044.9 and 5058.9 mg/day.</p

Odds ratio (OR) for obesity risk by quintiles of residual-Na were estimated in boys (A) and girls (B).

<p>X-axis means the quintiles of sodium intakes with energy adjustments, Y-axis means OR for obesity risk and bars described. OR in each genotype of gene (lighter; wild homozygote, meddle; heterozygote, darker; mutant homozygote). In case of <i>SLC12A3</i>, darker block was described by combination of mutant and hetero because of few mutant frequencies. Statistically significances by p<0.05(*) were shown above bars. Means of the residual-Na in each quintile for boys are 2402.9, 3122.2, 3630.7, 4202.8 and 5194.1 mg/day. Means of residual-Na in each quintile for girls are 2190.8, 2878.4, 3378.9, 3882.5 and 4889.3 mg/day. [Abbreviation: angiotensin converting enzyme; <i>ACE</i>, cytochrome P450, family 11 subfamily B polypeptide 2;<i>CYP11β-2</i>, G protein-coupled receptor kinases type 4;<i>GRK4 A486V</i>, solute carrier family 12(sodium/chloride transporters)-member 3;<i>SLC12A3</i>.]</p