Joohyun Jung; Myoungsook Lee

doi:10.4163/jnh.2017.50.1.32

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

Research Article

J Nutr Health 2017;50(1):32-40.

Published online: 20 January 2017

DOI: https://doi.org/10.4163/jnh.2017.50.1.32

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

Joohyun Jung¹, Myoungsook Lee^2,^†

¹Department of Food and Nutrition, Sungshin Women's University, Seoul 01133, Korea

²Research Institute of obesity Sciences, Sungshin Women's University, Seoul 01133, Korea

^†To whom correspondence should be addressed. tel: +82-2-920-7211, E-mail: mlee@sungshin.ac.kr

^∗ This work was supported by the National Research Foundation of Korean (NRF) grant funded by the Korea government (MSIP:2014R1A2A1A11049611/1).

Received 11 January 2017 Revised 23 January 2017 Accepted 2 February 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: children obesity, sodium intake, salt sensitive gene, SLC12A3

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Fig. 1.

Experimental design of the cross-sectional study

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.

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.

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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