The Assessment of TLR1 Gene Polymorphism Association with the Risk of Allergic Rhinitis in the Chinese Han Population from Northern China

Figures & data

Table 1 Characteristics of the AR Patients and Healthy Controls

Variables	Cases (n = 982)	Control (n = 984)
Age (mean ± SD, years)	42.43 ± 10.39	43.62 ± 8.05
> 43	486(49.5%)	561(57.0%)
≤ 43	496(50.5%)	423(43.0%)
Gender
Male	357(36.4%)	344(35.0%)
Female	625(63.6%)	640(65.0%)
BMI (kg/m^2)	24.78 ± 3.61	24.87 ± 3.66
> 24	495(50.4%)	520(52.8%)
≤ 24	487(49.6%)	464(47.2%)
Region
Wind beach region	245(24.9%)	270(27.4%)
Loess hilly region	737(75.1%)	714(72.6%)

Abbreviations: SD, standard deviation; AR, allergic rhinitis; BMI, body mass index.

Table 2 Basic Information of the SNPs in TLR1 Gene

SNP	Gene	Chromosome	Allele (minor/major)	MAF		HWE	HaploReg
				Case	Control	P
rs72493538	TLR1	4p14	A/G	0.061	0.078	0.507	SiPhy cons; Enhancer histone marks
rs76600635	TLR1	4p14	G/A	0.059	0.077	0.650	Enhancer histone marks; Motifs changed
rs17616434	TLR1	4p14	T/C	0.365	0.350	0.079	Enhancer histone marks; Motifs changed; NHGRI/EBI GWAS hits; Selected eQTL hits

Note: P values were calculated by χ² test.

Abbreviations: SNP, single nucleotide polymorphism; MAF, minor allele frequency; HWE, Hardy-Weinberg equilibrium.

Table 3 Associations Between TLR1 Polymorphisms and AR Susceptibility

SNP	Model	Genotype	Control	Case	OR (95% CI)	p-value
rs72493538	Allele	A	1812 (96.2%)	1844 (93.9%)	1.00
		G	154 (3.8%)	120 (6.1%)	0.77 (0.60–0.98)	0.034
	Codominant	G/G	833 (84.7%)	869 (88.5%)	1.00
		A/G	146 (14.8%)	106 (10.8%)	0.70 (0.54–0.92)	0.011
		A/A	4 (0.4%)	7 (0.7%)	1.67 (0.48–5.74)	0.418
	Dominant	G/G	833 (84.7%)	869 (88.5%)	1.00
		A/G-A/A	150 (15.3%)	113 (11.5%)	0.73 (0.56–0.95)	0.019
	Recessive	G/G-A/G	979 (99.6%)	975 (99.3%)	1.00
		A/A	4 (0.4%)	7 (0.7%)	1.75 (0.51–6.02)	0.375
	Additive	---	---	---	0.78 (0.61–0.99)	0.044
rs76600635	Allele	A	1815 (92.3%)	1845 (94.1%)	1.00
		G	151 (7.7%)	115 (5.9%)	0.75 (0.58–0.96)	0.024
	Codominant	A/A	836 (85%)	870 (88.8%)	1.00
		A/G	143 (14.6%)	105 (10.7%)	0.71 (0.54–0.93)	0.014
		G/G	4 (0.4%)	5 (0.5%)	1.17 (0.31–4.36)	0.821
	Dominant	A/A	836 (85%)	870 (88.8%)	1.00
		A/G-G/G	147 (14.9%)	110 (11.2%)	0.72 (0.56–0.94)	0.017
	Recessive	A/A-A/G	979 (99.6%)	975 (99.5%)	1.00
		G/G	4 (0.4%)	5 (0.5%)	1.22 (0.33–4.56)	0.771
	Additive	---	---	---	0.75 (0.58–0.97)	0.028
rs17616434	Allele	C	1274 (65.0%)	1246 (63.5%)	1.00
		T	686 (35%)	716 (36.5%)	1.07 (0.94–1.22)	0.329
	Codominant	C/C	401 (40.9%)	401 (40.9%)	1.00
		C/T	472 (48.2%)	444 (45.3%)	0.93 (0.77–1.13)	0.474
		T/T	107 (10.9%)	136 (13.9%)	1.26 (0.95–1.69)	0.113
	Dominant	C/C	401 (40.9%)	401 (40.9%)	1.00
		C/T-T/T	579 (59.1%)	580 (59.1%)	0.99 (0.83–1.19)	0.946
	Recessive	C/C-C/T	873 (89.1%)	845 (86.1%)	1.00
		T/T	107 (10.9%)	136 (13.9%)	1.31 (1.00–1.72)	0.050
	Additive	---	---	---	1.06 (0.93–1.21)	0.362

Notes: p values were calculated by χ² test after adjustment for age, gender, and BMI. Bold values indicate statistical significance (p < 0.05).

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; CI, confidence interval.

Figure 1 Positive results about TLR1-rs72493538 and -rs76600635 found in stratified analysis are shown in forest map.

Table 4 SNP-SNP Interactions of TLR1 Gene Analyzed by MDR Method

Model	Bal. Acc. Training	Bal. Acc. Testing	CVC	OR (95% CI)	p
rs72493538	0.522	0.507	8/10	1.45 (1.11–1.90)	0.006
rs72493538, rs76600635	0.538	0.536	10/10	1.85 (1.43–2.40)	< 0.0001
rs72493538, rs76600635, rs17616434	0.542	0.524	10/10	2.46 (1.81–3.35)	< 0.0001

Notes: p values were calculated using χ² tests. p < 0.05 and bold text indicate there are statistical significance.

Abbreviations: MDR, multifactor dimensionality reduction; Bal. Acc., balanced accuracy; CVC, cross–validation consistency; OR, odds ratio; CI, confidence interval.

Figure 2 Multifactor dimensionality reduction (MDR) analysis of interaction between the four SNPs of TLR1 (rs72493538, rs76600635, and rs17616434). (A) The color represents the degree of redundancy or synergy between SNP-SNP; the closer the color is to red, the more synergy, and the closer to blue, the more redundancy; (B) The Fruchterman-Region of SNP-SNP interactions. Each SNP is reported in per cent the value of Information Gain (IG), while numbers in the connections indicate the entropy-based IG for the SNP pairs. Red bar indicates high-level synergies on the phenotype, while blue connections with negative IG values indicate redundancy or lack of synergistic interactions between the markers.