Association of Vitamin D Receptor Gene Polymorphisms with Metabolic Syndrome in Chinese Children

Figures & data

Table 1 The Clinical and Biochemical Profiles of Subjects

	Overweightness/Obesity	Controls	P
N (male/female)	106 (70/36)	86 (60/26)	0.583^a
Age (years)	10.83 ± 2.31	10.15 ± 2.53	0.050
BMI z-score	2.41 (1.78, 3.15)	−0.47 (−0.79, −0.19)	<0.001^b
WHt	0.58 (0.54, 0.61)	0.42 (0.40, 0.44)	<0.001^b
SBP (mmHg)	117.56 ± 9.77	106.30 ± 8.03	<0.001
DBP (mmHg)	69.22 ± 8.75	65.70 ± 7.47	0.004
FBG (mmol/L)	5.30 ± 0.74	5.17 ± 0.30	0.100
TG (mmol/L)	1.26 ± 0.67	0.68 ± 0.26	<0.001
TC (mmol/L)	4.11 ± 0.62	3.79 ± 0.56	<0.001
LDL-C (mmol/L)	2.33 ± 0.54	1.76 ± 0.41	<0.001
HDL-C (mmol/L)	1.27 ± 0.27	1.45 ± 0.24	<0.001
25(OH)D (ng/mL)	18.44 ± 6.50	21.83 ± 7.32	0.001
N (Vitamin D deficiency)	68	41	0.022^a

Notes: The values are presented as mean ± SD or median (interquartile range). ^aP values were calculated using the Chi-square (X²) test. ^bP values were calculated using the Mann–Whitney U-test.

Abbreviations: BMI, body mass index; WHtR, waist-to-height ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; TG, triglycerides; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; 25(OH)D, 25-hydroxyvitamin D; SD, standard deviation.

Table 2 Genotypes and Allele Frequencies of the Studied SNPs

SNPs	Alleles (A/a)	SN Location	Chr 12 Position	Patients (n)	Genotype Frequencies			Allelic Frequencies
			(GRCh38.p12)		AA	Aa	aa	A	a
rs731236 (TaqI)	T/C	exon	47,844,974	191	166 (86.5)	23 (12.0)	2 (1.0)	0.93	0.07
rs7975232 (ApaI)	C/A	intron	47,845,054	190	94 (49.0)	80 (41.7)	16 (8.3)	0.71	0.29
rs1544410 (BsmI)	G/A	intron	47,846,052	190	160 (83.3)	27 (14.1)	3 (1.6)	0.91	0.09
rs2228570 (FokI)	G/A	exon	47,879,112	180	51 (26.6)	91 (47.4)	38 (19.8)	0.54	0.46
rs11568820 (Cdx2)	G/A	promoter	47,908,762	191	61 (31.8)	88 (45.8)	42 (21.9)	0.55	0.45

Note: “A” represents the major allele, while “a” represents the minor allele.

Abbreviations: SNP, single-nucleotide polymorphism; VDR, vitamin D receptor.

Table 3 Distribution of SNP Genotypes and Allele Frequencies Between Overweight/Obese Children and Healthy Controls

SNPs	Genotype/Allele	Overweightness/Obesity	Controls	P^a	OR	95% CI	P^b
TaqI	TT	92 (86.8%)	74 (87.1%)	0.547	1
	TC	12 (11.3%)	11 (12.9%)		0.88	0.37–2.10	0.769
	CC	2 (1.9%)	0		/	/	/
	T	196 (92.5%)	159 (93.5%)		1
	C	16 (7.5%)	11 (6.5%)		1.18	0.53–2.62	0.683
ApaI	CC	50 (47.6%)	44 (51.8%)	0.984	1
	CA	41 (39.0%)	39 (45.9%)		0.93	0.51–0.68	0.798
	AA	14 (13.3%)	2 (2.4%)		6.16	1.33–28.62	0.010
	C	141 (67.1%)	127 (74.7%)		1
	A	69 (32.9%)	43 (25.3%)		1.45	0.92–2.27	0.108
BsmI	GG	92 (86.8%)	68 (81.0%)	0.603	1
	GA	11 (10.4%)	16 (19.0%)		0.51	0.22–1.16	0.105
	AA	3 (2.8%)	0		/	/	/
	G	195 (92.0%)	152 (90.5%)		1
	A	17 (8.0%)	16 (9.5%)		0.83	0.41–1.69	0.605
FokI	GG	28 (26.7%)	23 (30.7%)	0.976	1
	GA	52 (49.5%)	39 (52.0%)		1.10	0.55–2.18	0.796
	AA	25 (23.8%)	13 (17.3%)		1.58	0.66–3.76	0.301
	G	108 (51.4%)	85 (56.7%)		1
	A	102 (48.6%)	65 (43.3%)		1.24	0.81–1.88	0.326
Cdx2	GG	33 (31.1%)	28 (32.9%)	0.631	1
	GA	49 (46.2%)	39 (45.9%)		1.07	0.55–2.06	0.848
	AA	24 (22.6%)	18 (21.2%)		1.13	0.51–2.50	0.760
	G	115 (54.2%)	95 (55.9%)		1
	A	97 (45.8%)	75 (44.1%)		1.07	0.71–1.60	0.749

Notes: ^aP-value for HWE test in both groups. ^bP-value for OR.

Abbreviations: HWE, Hardy-Weinberg equilibrium; OR, odds ratio; SNP, single-nucleotide polymorphism; CI, confidence interval.

Table 4 SNP Genotype Distributions and Risk Assessments for Metabolic Syndrome and Its Components with Vitamin D Deficiency, Using Genetic Models

SNPs/Models	Genotypes	Metabolic Syndrome		Abdominal Obesity		Increased Plasma Glucose		High Blood Pressure		Low HDL-C		Elevated TG		Vitamin D Deficiency
		OR	P	OR	P	OR	P	OR	P	OR	P	OR	P	OR	P
ApaI
Dominant	CC	1		1		1		1		1		1		1
	CA+AA	0.73	0.540	1.01	0.975	0.57	0.161	2.83	0.137	0.85	0.745	0.74	0.481	1.21	0.519
Recessive	CC+CA	1		1		1		1		1		1		1
	AA	1.85	0.406	4.01	0.039	3.88	0.020	1.18	0.878	1.46	0.641	1.59	0.496	2.84	0.120
FokI
Dominant	GG	1		1		1		1		1		1		1
	AA+GA	0.91	0.865	1.45	0.278	1.06	0.901	0.29	0.056	1.15	0.802	1.03	0.949	0.97	0.931
Recessive	GG+GA	1		1		1		1		1		1		1
	AA	3.07	0.045	1.32	0.476	1.59	0.305	1.48	0.585	1.51	0.477	1.64	0.316	0.51	0.069
Cdx2
Dominant	GG	1		1		1		1		1		1		1
	AA+GA	0.53	0.215	1.05	0.886	0.67	0.310	0.85	0.803	1.48	0.485	0.56	0.193	0.74	0.351
Recessive	GG+GA	1		1		1		1		1		1		1
	AA	1.07	0.912	1.18	0.640	1.38	0.466	0.31	0.269	1.63	0.372	1.40	0.495	0.60	0.148
TaqI
Dominant	TT	1		1		1		1		1		1		1
	CC+TC	0.78	0.758	0.80	0.615	0.74	0.644	2.07	0.390	0	0.998	2.80	0.057	0.93	0.869
BsmI
Dominant	GG	1		1		1		1		1		1		1
	AA+GA	1.08	0.910	0.51	0.119	0.78	0.674	1.42	0.671	0.31	0.270	2.00	0.189	0.93	0.857

Note: P-values were calculated using the multivariate logistic regression analysis model, which included age.

Abbreviations: SNP, single-nucleotide polymorphism; HDL-C, high-density lipoprotein cholesterol; TG, triglycerides.

Table 5 Haplotype Analysis Results Between Overweight/Obese and Healthy Children

Haplotypes (TaqI-ApaI-BsmI -FokI-Cdx2)	Frequency n (%)		OR	95% CI	P
	Overweight/Obesity Children	Controls
T-A-G-G-A	14.22 (6.8)	5.48 (3.9)	1.808	0.246	0.657 ~ 4.973
T-A-G-G-G	16.63 (8.0)	13.91 (9.8)	0.786	0.529	0.371 ~ 1.665
T-A-G-A-A	17.08 (8.2)	5.36 (3.8)	2.261	0.101	0.834 ~ 6.133
T-A-G-A-G	7.77 (3.7)	6.98 (4.9)	0.740	0.572	0.259 ~ 2.109
T-C-G-G-A	29.50 (14.2)	22.57 (15.9)	0.859	0.620	0.471 ~ 1.566
T-C-G-G-G	32.78 (15.8)	33.44 (23.5)	0.590	0.056	0.342 ~ 1.017
T-C-G-A-A	28.04 (13.5)	20.37 (14.3)	0.915	0.778	0.492 ~ 1.701
T-C-G-A-G	43.98 (21.1)	19.89 (14.0)	1.637	0.097	0.912 ~ 2.938

Abbreviations: OR, odds ratio; CI, confidence interval.

Figure 1 Plot showing the linkage disequilibrium (LD) among vitamin D receptor (VDR) gene polymorphisms in D’ values.

Note: The red square indicates high linkage disequilibrium.