Journal List > J Nutr Health > v.50(1) > 1081508

Jung and Lee: Effects of interaction between SLC12A3 polymorphism, salt-sensitive gene, and sodium intake on risk of child obesity∗

Abstract

Purpose

Obesogenic environments in children, in particular excessive intake of sodium, generate hypertension, which is a major risk factor for chronic diseases. Methods: In all, 725 children, 379 boys and 373 girls, aged 8∼9 years were recruited from seven elementary schools in Kuro-ku, Seoul. To evaluate whether or not obesity risk was modulated by salt-sensitive genes, Solute Carrier Familiy 12 member 3 (SLC12A3) was used as the target. After children were assigned into obese (BMI > 85 percentile) or non-obese groups, anthropometry, blood biochemistry, and dietary intakes were measured according to the genotypes GG (wild) or GA+AA (hetero+mutant). Results: Without gender differences, high TG and low HDLc were detected in the obese group compared to the non-obese group. Regardless of obesity, weight gain and blood pressure (BP) increased in the SLC12A3 GA+AA genotype rather than in the GG type. HDLc was associated with obesity risk without genotype difference. Odd ratios for risk of obesity were 15.57 (95% CI 2.192∼110.654), 22.84 (95% CI 1.565∼333.469), and 9.32 (95%CI 1.262∼68.817) in boys and girls with GA+AA genotypes as sodium intake increased above 4,000 mg/day. Dietary calcium, sodium, folate, and vit C were associated with obesity risk according to gender or genotype differences. Since high folate intake reduced obesity risk in only boys with GG type. Risk for overweight and obesity increased in boys with GA+AA genotypes and dietary habits with high sodium and cholesterol and low folate. Conclusion: The A allele of SLC12A3 rs11643718 was sensitive to development of obesity in children as sodium intake increased.

References

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Fig. 1.
Experimental design of the cross-sectional study
jnh-50-32f1.tif
Fig. 2.
Odd ratio of the risk of obesity by categories of plasma HDLc and insulin levels according to SLC12A3 genotypes, GG vs GA + AA. Categories of HDLc levels or in each tertiles of total subjects are > 51.92, 51.92 ∼ 60.34, ≥ 60.35 mg/day, insulin levels in each tertile are < 4.40, 4.41 ∼ 7.33, ≥ 7.34 mg/day.
jnh-50-32f2.tif
Fig. 3.
Odd ratio of the risk of obesity by categories of dietary factors according to SLC12A3 genotypes, GG vs GA + AA. Categories of dietary intakes in each tertile are < 288.48, 288.48 ∼ 387.55, ≥ 387.56 mg/day for cholesterol, and < 206.54, 206.54 ∼ 266.11, ≥ 266.12 ug/ day for folate, and < 3,326.73, 3,326.73 ∼ 3955, ≥ 3,955.01 mg/day for sodium.
jnh-50-32f3.tif
Table 1.
Relative frequencies of SLC12A3 rs11643718 genotypes in obese and non-obese boys and girls
  Total Boy Girl
  non-OB OB1) non-Ob OB non-OB OB
GG 530 (84.4)2) 98 (15.6) 262 (82.1) 57 (17.9) 268 (86.7) 41 (13.3)
GA + AA 93 (75.0) 31 (25.0) 42 (70.0) 18 (30.0) 51 (79.7) 13 (20.3)
P-value 0.011 0.030 0.145

1) Obesity classification by BMI percentiles; obesity ≥ 95 percentile, 85 percentile ≤ overweight < 95 percentile, normal < 85 percentile for Korean children obesity criteria from Korean society of obesity. In this obese (OB) group, the overweight group was included. 2) Number of subjects (%)

Table 2.
Anthropometry and blood biochemistry in obese and non-obese boys and girls according to SLC12A3 rs11643718 genotypes
    Total       Boy       Girl    
  Non-OB OB   Non-OB OB   Non-OB OB  
  GG (n = 530) GA + AA (n = 93) GG (n = 98) GA + AA (n = 31) P1) A GG (n = 262) GA + AA (n = 42) GG (n = 57) GA + AA (n = 18) P1) A ( GG (n = 268) GA + AA (n = 51) GG (n = 41) GA + AA (n = 13) P1)
  Mean (SD) Mean (SD)   Mean (SD) Mean (SD)   Mean (SD) Mean (SD)  
Anthropometric Measurements
Height (cm) 131.09+ (5.32) 131.83+ (5.56) 135.02+ (5.07) 135.21+ (6.54) < 0.001 131.64+ (5.21) 132.09++ (5.06) 135.77++ (4.84) + 138.04++ (6.85) < 0.001 130.55+ (5.38) 131.62 (5.98) 133.98+ (5.26) 131.3 (3.44) 0.002
Weight (kg) 28.48 (3.88) 29.39∗+ (4.26) 40.26+ (5.72) 39.14+ (5.63) < 0.001 29.14+ (3.86) 29.8+ ±(4.11) 41.53+ (5.67) 41.84+ (5.74) < 0.001 27.84∗+ (3.8) 29.06∗+ (4.4) 38.49∗+ (5.37) 35.41∗+ (2.58) < 0.001
WC (cm) 55.78+ (5.21) 56.69+ (4.75) 68.23+ (7.17) 66.87+ (6.44) < 0.001 57.28+ (5.61) 57.82+ (5.11) 70.63+ (7.73) 69.3+ (6.51) < 0.001 54.32∗+ (4.32) 55.75∗+ (4.25) 64.9+ (4.64) 63.5+ (4.73) < 0.001
BMI (kg/m2) 16.52+ (1.52) 16.85+ (1.66) 22+ (2.15) 21.33+ (1.82) < 0.001 16.76+ (1.5) 17.03+ (1.67) 22.46+ (2.11) 21.88+ (1.74) < 0.001 16.29+ (1.5) 16.7+ (1.66) 21.37+ (2.07) 20.56+ (1.69) < 0.001
            Lipid profiles              
AST (IU/L) 24.46 (5.01) 24.17 (5.53) 24.7 (6.46) 23.23 (3.95) NS 24.9 (4.89) 24.5 (6.03) 25.3 (6.46) 23.89 (4.54) NS 24.03 (5.1) 23.9 (5.12) 23.88 (6.46) 22.31 (2.87) NS
ALT (IU/L) 20.18+ (4.79) 20.04+ (4.3) 26.5+ (13.57) 24.32+ (5.42) < 0.001 20.68+ (4.81) 20.55+ (4.17) 28.12+ (13.87) 25.06+ (5.45) < 0.001 17.69+ (4.73) 19.63+ (4.4)+ 24.24+ (12.98)+ 23.31+ (5.42)+ < 0.001
SBP (mmHg) 108.15∗+ (16.59) 113.13∗+ (17.58) 116.55∗+ (20.9) 125.35∗+ (21.78) < 0.001 109.76+ (16.58) 112.6+ (17.32) 120.98+ (19.59) 124.94+ (19.92) < 0.001 106.59 (16.48) 113.57+ (17.95) 110.39 (21.33) 125.92∗∗ (24.96) < 0.001
DBP (mmHg) 68.91∗+ (14.02) 74.41∗+ (16.22) 74.95∗+ (15.57) 81.39∗+ (15.84) < 0.001 69.3∗+ (13.87) 74.76+ (16.94) 78.14+ (15.89) 81.06 (14.56) < 0.001 68.52 (14.18) 74.12 (15.78) 70.51 (14.13) 81.85 (18.07) 0.002
TC (mg/dl) 177.63 (30.38) 179.62 (36.26) 183.68 (30.59) 187.03 (32.16) NS 176.78 (29.4) 176.69 (33.97) 182 (32.23) 182.78 (30.53) NS 178.47 (31.35) 182.04 (38.2) 186.02 (28.39) 192.92 (34.65) NS
TG (mg/dl) 68.87+ (31.81) 75.33+ (44.74) 85.32∗+ (47.8) 93.71∗+ (44.1) < 0.001 65.19+ (29.98) 73.55 (57.91) 77.56+ (42.09) 82.83 (37.26) 0.027 72.47+ (33.17) 76.8 (30.47) 96.1+ (53.44) 108.77+ (49.73) < 0.001
LDL (mg/dl) 106.47 (28.32) 106.11 (33.88) 114+ (28.2) 116.5 (31.54) 0.036 105.55 (27.36) 103.74 (30.62) 112.53 (29.64) 112.01 (34.06) NS 107.36 (29.26) 108.06 (36.53) 116.03 (26.29) 122.71 (27.78) NS
HDL (mg/dl) 57.39+ (10.18) 58.45+ (12.3) 52.62∗+ (9.39) 51.79∗+ (9.47) < 0.001 58.19+ (9.73) 58.24+ 13.55) 53.96+ (10.48) 54.2+ (7.08) 0.019 56.61+ (10.56) 58.62+ (11.31) 50.77+ (7.33) 48.46+ (11.52) < 0.001
Blood sugar related profiles
FBS (mg/dl) 74.87 (6.75) 75.18 (6.46) 76.18 (6.69) 75.42 (6.92) NS 76.24 (6.86) 77.29 (7.35) 76.56 (6.41) 74 (6.07) NS 73.53+ (6.38) 73.45 (5.08) 75.66+ (7.11) 77.38 (7.76) 0.043
Insulin (µIU/ml) 6.52+ (6.27) 7.72+ (6.93) 9.82∗+ (8.96) 8.92∗+ (4.91) < 0.001 6.68+ (7.82) 8.61 (7.28) 9.03+ (6.35) 8.81 (5.76) NS 6.36+ (4.24) 6.98 (6.62) 10.93+ (11.67) 9.08 (3.66) < 0.001
HOMA-IR 1.22+ (1.25) 1.45+ (1.41) 1.86∗+ (1.77) 1.68∗+ (0.94) < 0.001 1.28+ (1.61) 1.65 (1.49) 1.72+ (1.3) 1.63 (1.07) NS 1.15+ (0.75) 1.28 (1.33) 2.05+ (2.29) 1.75 (0.77) < 0.001

1) P-value: Significantly differences of indicators among the 4 groups in total, boys and girls, NS: non-significant (p > 0.05) ∗Significantly differences between GG and GA+AA in non-OB or OB groups (∗p < 0.05, ∗∗p < 0.01). Significantly differences between non-OB and OB groups in GG or GA+AA genotype (p < 0.05). Abbreviation: WC, waist circumferences; BMI, body mass index; AST, aspartate transaminase; ALT, alanine transaminase; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triacylglycrides; HDLc, high-density lipoprotein cholesterol; LDLc, low-density lipoprotein cholesterol; FBS, fasting blood glucose; HOMA-IR, homeostasis model assessment of insulin resistance

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