The Impacts of IL1R1 and IL1R2 Genetic Variants on Rheumatoid Arthritis Risk in the Chinese Han Population: A Case–Control Study

Figures & data

Table 1 Basic Characteristics of Both Cases and Controls

Variables	RA Patients (n = 508)		Controls (n = 494)		p
	Count(%)	Mean ± SD	Count (%)	Mean ± SD
Gender					p^a > 0.05
Male	134 (26%)		124 (25%)
Female	374 (74%)		370 (75%)
Age, years (Mean ± SD)		54.34 ± 12.01		54.03 ± 8.83	p^b < 0.001
>54	261 (51%)		253 (51%)
≤54	247 (49%)		241 (49%)
CRP (mg/L)	508 (100%)	30.83% ± 40.23
RF (KIU/L)	508 (100%)	164.95 ± 147.26
ESR (mm/hr)	508 (100%)	44.15 ± 30.68
CCP (RU/mL)	508 (100%)	136 ± 76.12
AKA (%)	508 (100%)
Positive	122 (24%)
Weak positive	46 (9%)
Negative	340 (67%)

Notes: p^a was calculated by Chi-square test. p^b was calculated by Student’s t-test, p < 0.05 indicates statistical significance. The 54 year was determined by the Mean ± SD value of age in RA patients and control groups.

Abbreviations: CCP, anti-cyclic citrullinated peptide; CRP, C-reaction protein; ESR, erythrocyte sedimentation rate; RA, rheumatoid arthritis; RF, rheumatoid factor; SD, standard deviation.

Table 2 The Result of Distribution Analysis of Allele Frequencies of IL1R1/IL1R2 SNPs in Case and Control Groups

Gene	SNP	Chromosome Position (bp)	Alleles	MAF		O(HET)	E(HET)	HWE- p^a	OR (95% CI)	p^b
			(A/B)	Control	RA Patients
IL1R1	rs10490571	Chr2:102,100,877	A/G	0.178	0.204	0.311	0.325	0.879	1.18 (0.94–1.48)	0.145
	rs956730	Chr2:102,141,656	A/G	0.242	0.231	0.453	0.439	0.903	0.94 (0.77–1.16)	0.574
	rs3917225	Chr2:102,152,842	A/G	0.359	0.363	0.397	0.416	0.626	1.02 (0.85–1.22)	0.877
	rs3917318	Chr2:102,176,300	A/G	0.49	0.475	0.229	0.236	0.176	0.94 (0.79–1.12)	0.516
IL1R2	rs11674595	Chr2:101,994,530	C/T	0.204	0.227	0.358	0.358	0.333	1.14 (0.92–1.42)	0.223
	rs4851527	Chr2:102,005,914	A/G	0.326	0.297	0.298	0.317	0.539	0.87 (0.72–1.06)	0.166
	rs719250	Chr2:102,007,256	A/G	0.296	0.258	0.292	0.293	0.282	0.83 (0.68–1.01)	0.064
	rs3218896	Chr2:102,015,190	C/T	0.137	0.123	0.37	0.367	0.451	0.88 (0.68–1.15)	0.356
	rs3218977	Chr2:102,024,739	A/G	0.234	0.257	0.472	0.46	1	1.13 (0.92–1.39)	0.23
	rs2072472	Chr2:102,026,557	C/T	0.197	0.23	0.469	0.5	0.2	1.22 (0.98–1.51)	0.072

Notes: OR (95% CI): Calculated by unconditional logistic regression adjusted by gender and age. HWE- p^aCalculated by Fisher’s exact test, p^bCalculated by Pearson’s Chi-square test.

Abbreviations: RA, rheumatoid arthritis; IL1R1, interleukin-1 receptor 1; IL1R2, interleukin-1 receptor 2; SNP, single-nucleotide polymorphism; Position (bp), Genomic position (NCBI Build 36), A/B, minor/major alleles on the control sample frequencies, MAF, minor allele frequency; O(HET), observed heterozygosity; E(HET), expected heterozygosity; HWE, Hardy–Weinberg equilibrium; OR, odds ratio; 95% CI, 95% confidence interval.

Table 3 Association Analysis Result Between IL1R2 Rs2072472 Genetic Variants and Rheumatoid Arthritis Risk

Gene	SNP	Model	Genotype	RA Patients	Control	OR (95% CI)	p	FDR Test
				n (Freq)	n (Freq)
IL1R2	rs2072472	Allele	G	234 (23.03%)	195 (19.74%)	1
			A	782 (76.97%)	793 (80.26%)	1.22 (0.98–1.51)	0.072	0.360
		Codominant	A/A	296 (58.27%)	323 (65.38%)	1
			A/G	190 (37.40%)	147 (29.76%)	1.41 (1.08–1.84)	0.011	0.275
			G/G	22 (4.33%)	24 (4.86%)	1.00 (0.55–1.82)	1	1.000
		Dominant	A/A	296 (58.27%)	323 (65.38%)	1
			A/G-G/G	212 (41.73%)	171 (34.62%)	1.35 (1.05–1.75)	0.021	0.350
		Recessive	A/G-A/A	486 (95.67%)	470 (95.14%)	1
			G/G	22 (4.33%)	24 (4.86%)	0.89 (0.49–1.60)	0.688	1.011
		Log-additive	-	-	-	1.22 (0.98–1.51)	0.073	0.608

Notes: OR (95% CI): Calculated by unconditional logistic regression adjusted by gender and age. p - value was calculated by two -sided χ² test. Bold means statistical significance.

Abbreviations: RA, rheumatoid arthritis; IL1R2, interleukin-1 receptor 2; SNP, single-nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval; FDR, false discovery rate; freq, frequency.

Table 4 Association Analysis Result Between IL1R1/ IL1R2 Genetic Variants and Rheumatoid Arthritis Risk Based on the Gender Stratification

Gene	SNP	Genotype	Model	Males		OR (95% CI)	p	FDR Test	Females		OR (95% CI)	p	FDR Test
				RA Patients n (Freq)	Control n (Freq)				RA Patients n (Freq)	Control n (Freq)
IL1R1	rs3917318	Allele	G	113 (42.16%)	127 (51.21%)	1			377 (50.54%)	382 (51.76%)	1
			A	155 (57.84%)	121 (48.79%)	1.44 (1.02–2.04)	0.040	0.200	369 (49.46%)	356 (48.24%)	1.05 (0.86–1.29)	0.637	0.796
		Codominant	G/G	26 (19.40%)	38 (30.65%)	1			93 (24.93%)	101 (27.37%)	1
			G/A	61 (45.52%)	51 (41.13%)	1.97 (1.01–3.83)	0.045	0.450	191 (51.21%)	180 (48.78%)	1.15 (0.81–1.63)	0.427	1.334
			A/A	47 (35.07%)	35 (28.23%)	1.76 (0.94–3.27)	0.077	0.275	89 (23.86%)	88 (23.85%)	1.10 (0.73–1.65)	0.651	1.085
		Dominant	G/G	26 (19.40%)	38 (30.65%)	1			93 (24.93%)	101 (27.37%)	1
			G/A-A/A	108 (80.60%)	86 (69.35%)	1.84 (1.04–3.27)	0.037	0.463	280 (75.07%)	268 (72.63%)	1.13 (0.81–1.57)	0.452	1.189
		Recessive	G/A-G/G	87 (64.93%)	89 (71.77%)	1			329 (88.20%)	324 (87.57%)	1
			A/A	47 (35.07%)	35 (28.23%)	1.38 (0.81–2.33)	0.237	0.515	44 (11.80%)	46 (12.43%)	1.00 (0.71–1.40)	0.992	0.992
		Log-additive	–	–	–	1.39 (1.00–1.93)	0.053	0.294	–	–	1.00 (0.86–1.29)	0.636	1.097
	rs10490571	Allele	C	203 (75.75%)	120 (82.66%)	1			606 (81.02%)	607 (82.03%)	1
			T	65 (24.25%)	43 (17.34%)	1.53 (0.99–2.35)	0.065	0.217	142 (18.98%)	133 (17.97%)	1.07 (0.82–1.39)	0.615	0.879
		Codominant	C/C	77 (57.46%)	86 (69.35%)	1			241 (64.44%)	248 (67.03%)	1
			C/T	49 (36.57%)	33 (26.61%)	1.66 (0.97–2.84)	0.065	0.271	124 (33.16%)	111 (30.00%)	1.14 (0.84–1.57)	0.398	1.327
			T/T	8 (5.97%)	5 (4.03%)	1.84 (0.57–5.97)	0.307	0.512	9 (2.41%)	11 (2.97%)	0.84 (0.34–2.06)	0.698	1.058
		Dominant	C/C	77 (57.46%)	86 (69.35%)	1			241 (64.44%)	248 (67.03%)	1
			C/T-T/T	57 (42.54%)	38 (30.65%)	1.68 (1.01–2.81)	0.047	0.392	133 (35.56%)	122 (32.97%)	1.12 (0.82–1.51)	0.477	1.193
		Recessive	C/T-C/C	126 (94.03%)	119 (95.97%)	1			365 (97.59%)	359 (97.03%)	1
			T/T	8 (5.97%)	5 (4.03%)	1.56 (0.49–4.97)	0.454	0.649	9 (2.41%)	11 (2.97%)	0.80 (0.33–1.96)	0.624	1.156
		Log-additive	–	–	–	1.52 (0.99–2.33)	0.056	0.255	–	–	1.07 (0.82–1.40)	0.63	1.125
	rs956730	Allele	G	200 (75.19%)	184 (74.19%)	1			578 (77.48%)	565 (76.35%)	1
			A	66 (24.81%)	64 (25.81%)	0.95 (0.64–1.41)	0.796	0.884	168 (22.52%)	175 (23.65%)	0.94 (0.74–1.20)	0.606	1.010
		Codominant	G/G	75 (56.39%)	64 (51.61%)	1			217 (58.18%)	219 (59.19%)	1
			G/A	50 (37.59%)	56 (45.16%)	0.76 (0.46–1.26)	0.288	0.533	144 (38.61%)	127 (34.32%)	1.14 (0.84–1.55)	0.388	1.386
			A/A	8 (6.02%)	4 (3.23%)	1.70 (0.49–5.91)	0.406	0.615	12 (3.22%)	24 (6.49%)	0.50 (0.24–1.03)	0.061	0.610
		Dominant	G/G	75 (56.39%)	64 (51.61%)	1			217 (58.18%)	219 (59.19%)	1
			G/A-A/A	58 (43.61%)	60 (48.39%)	0.82 (0.50–1.35)	0.434	0.638	156 (41.82%)	151 (40.81%)	1.04 (0.78–1.40)	0.785	0.957
		Recessive	G/A-G/G	125 (93.98%)	120 (96.77%)	1			365 (97.59%)	359 (97.03%)	1
			A/A	8 (6.02%)	4 (3.23%)	1.92 (0.56–6.54)	0.298	0.514	9 (2.41%)	11 (2.97%)	0.48 (0.24–0.97)	0.042	0.700
		Log-additive	–	–	–	0.94 (0.62–1.43)	0.777	0.883	–	–	0.94 (0.73–1.2)	0.596	1.146
IL1R2	rs719250	Allele	C	204 (76.12%)	168 (67.74%)	1			545 (73.45%)	528 (71.35%)	1
			T	64 (23.88%)	80 (32.26%)	0.66 (0.45–0.97)	0.034	0.340	197 (26.55%)	212 (28.65%)	0.90 (0.72–1.13)	0.366	0.915
		Codominant	C/C	76 (56.72%)	58 (46.77%)	1			203 (54.72%)	192 (51.89%)	1
			C/T	52 (38.81%)	52 (41.94%)	0.76 (0.46–1.26)	0.288	0.533	139 (37.47%)	144 (38.92%)	0.91 (0.67–1.24)	0.559	1.215
			T/T	6 (4.48%)	14 (11.29%)	0.33 (0.12–0.91)	0.032	0.800	29 (7.82%)	34 (9.19%)	0.81 (0.47–1.38)	0.43	1.265
		Dominant	C/C	76 (56.72%)	58 (46.77%)	1			203 (54.72%)	192 (51.89%)	1
			C/T-T/T	58 (43.28%)	66 (53.23%)	0.67 (0.41–1.09)	0.109	0.341	168 (45.28%)	178 (48.11%)	0.89 (0.67–1.19)	0.441	1.225
		Recessive	C/T-C/C	128 (95.52%)	110 (88.71%)	1			342 (92.18%)	336 (90.81%)	1
			T/T	6 (4.48%)	14 (11.29%)	0.37 (0.13–0.99)	0.049	0.350	29 (7.82%)	34 (9.19%)	0.84 (0.50–1.41)	0.503	1.143
		Log-additive	–	–	–	0.66 (0.44–0.97)	0.036	0.600	–	–	0.90 (0.72–1.13)	0.377	1.450
	rs3218977	Allele	A	194 (72.39%)	185 (74.60%)	1			561 (75.00%)	572 (77.30%)	1
			G	74 (27.61%)	63 (25.40%)	1.12 (0.76–1.66)	0.570	0.713	187 (25.00%)	168 (22.70%)	1.14 (0.89–1.44)	0.299	0.997
		Codominant	A/A	67 (50.00%)	71 (57.26%)	1			204 (54.55%)	219 (59.19%)	1
			A/G	60 (44.78%)	43 (34.68%)	1.37 (0.94–2.00)	0.104	0.347	153 (40.91%)	134 (36.22%)	1.31 (0.90–1.90)	0.155	0.861
			G/G	7 (5.22%)	10 (8.06%)	0.45(0.20–1.00)	0.052	0.325	17 (4.55%)	17 (4.59%)	0.44 (0.90–6.63)	0.081
		Dominant	A/A	67 (50.00%)	71 (57.26%)	1			204 (54.55%)	219 (59.19%)	1
			A/G-G/G	67 (50.00%)	53 (42.74%)	1.17(0.82–1.68)	0.383	0.598	170 (45.45%)	151 (40.81%)	1.38 (0.96–1.98)	0.081	0.675
		Recessive	A/G-A/A	127 (94.78%)	114 (91.94%)	1			357 (95.45%)	353 (95.41%)	1
			G/G	7 (5.22%)	10 (8.06%)	0.40 (0.18–0.88)	0.023	1.150	17 (4.55%)	17 (4.59%)	2.18 (0.81–5.84)	0.123	0.769
		Log-additive	–	–	–	0.97 (0.73–1.30)	0.843	0.937	–	–	1.39 (1.01–1.90)	0.041	1.025
	rs2072472	Allele	A	206 (76.87%)	201 (81.05%)	1			576 (77.01%)	592 (80.00%)	1
			G	62 (23.13%)	47 (18.95%)	1.29 (0.84–1.97)	0.245	0.408	172 (22.99%)	148 (20.00%)	1.19 (0.93–1.53)	0.16	0.800
		Codominant	A/A	78 (58.21%)	82 (66.13%)	1			218 (58.29%)	241 (65.14%)	1
			A/G	50 (37.31%)	37 (29.84%)	1.43 (0.84–2.42)	0.184	0.460	140 (37.43%)	110 (29.73%)	1.41 (1.03–1.92)	0.031	1.550
			G/G	6 (4.48%)	5 (4.03%)	1.26 (0.37–4.30)	0.712	0.848	16 (4.28%)	19 (5.14%)	0.93 (0.47–1.85)	0.834	0.970
		Dominant	A/A	78 (58.21%)	82 (66.13%)	1			218 (58.29%)	241 (65.14%)	1
			A/G-G/G	56 (41.79%)	2 (33.87%)	1.41 (0.85–2.34)	0.185	0.440	156 (41.71%)	129 (34.86%)	1.34 (0.99–1.80)	0.056	0.700
		Recessive	A/G-A/A	128 (95.52%)	119 (95.97%)	1			358 (95.72%)	351 (94.86%)	1
			G/G	6 (4.48%)	5 (4.03%)	1.11 (0.33–3.75)	0.862	0.917	16 (4.28%)	19 (5.14%)	0.82 (0.42–1.63)	0.577	1.202
		Log-additive	–	–	–	1.30 (0.84–1.99)	0.238	0.496	–	–	1.19 (0.93–1.53)	0.164	0.820

Notes: OR (95% CI): Calculated by unconditional logistic regression adjusted by age. p - value was calculated by two -sided χ² test. Bold means statistical significance.

Abbreviations: RA, rheumatoid arthritis; IL1R1, interleukin-1 receptor 1; IL1R2, interleukin-1 receptor 2; SNP, single-nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval; FDR, false discovery rate; freq, frequency.

Table 5 Association Analysis Result Between IL1R1/ IL1R2 Genetic Variants and Rheumatoid Arthritis Risk Based on the Age Stratification

Gene	SNP	Genotype	Model	Age >54 Years		OR (95% CI)	p	FDR Test	Age ≤ 54 Years		OR (95% CI)	p	FDR Test
				RA Patients n (Freq)	Control n (Freq)				RA Patients n (Freq)	Control n (Freq)
IL1R1	rs956730	Allele	G	391 (75.48%)	375 (74.11%)	1			387 (78.34%)	374 (77.59%)	1
			A	127 (24.52%)	131 (25.89%)	0.93 (0.70–1.23)	0.613	1.226	107 (21.66%)	108 (22.41%)	0.96 (0.71–1.30)	0.778	0.778
		Codominant	G/G	138 (53.28%)	138 (54.55%)	1			154 (62.35%)	145 (60.17%)	1
			G/A	115 (44.40%)	99 (39.13%)	1.19 (0.83–1.72)	0.342	0.684	79 (31.98%)	84 (34.85%)	0.86 (0.58–1.26)	0.434	0.804
			A/A	6 (2.32%)	16 (6.32%)	0.40 (0.15–1.06)	0.065	0.361	14 (5.67%)	12 (4.98%)	1.28 (0.57–2.89)	0.549	0.885
		Dominant	G/G	138 (53.28%)	138 (54.55%)	1			154 (62.35%)	145 (60.17%)	1
			G/A-A/A	121 (46.72%)	115 (45.45%)	1.08 (0.76–1.55)	0.66	0.825	93 (37.65%)	96 (39.83%)	0.91 (0.63–1.31)	0.601	0.939
		Recessive	G/A-G/G	253 (97.68%)	237 (93.68%)	1			233 (94.33%)	229 (95.02%	1
			A/A	6 (2.32%)	16 (6.32%)	0.37 (0.14–0.97)	0.043	0.358	14 (5.67%)	12 (4.98%)	1.35 (0.61–3.02)	0.462	0.797
		Log-additive	–	–	–	0.95 (0.70–1.28)	0.720	0.837	–	–	0.98 (0.72–1.32)	0.881	0.937
IL1R2	rs4851527	Allele	G	360 (68.97%)	344 (67.98%)	1			354 (71.66%)	322 (66.80%)	1
			A	162 (31.03%)	162 (32.02%)	0.96 (0.73–1.24)	0.735	0.919	140 (28.34%)	160 (33.20%)	0.80 (0.61–1.05)	0.100	0.333
		Codominant	G/G	113 (43.30%)	119 (47.04%)	1			131 (53.04%)	102 (42.32%)	1
			G/A	134 (51.34%)	106 (41.90%)	1.32 (0.91–1.91)	0.148	0.435	92 (37.25%)	118 (48.96%)	0.63 (0.43–0.93)	0.019	0.950
			A/A	14 (5.36%)	28 (11.07%)	0.47 (0.23–0.96)	0.039	0.488	24 (9.72%)	21 (8.71%)	0.93 (0.49–1.78)	0.831	0.944
		Dominant	G/G	113 (43.30%)	119 (47.04%)	1			131 (53.04%)	102 (42.32%)	1
			G/A-A/A	148 (56.70%)	134 (52.96%)	1.13 (0.79–1.62)	0.490	0.766	116 (46.96%)	139 (57.68%)	0.68 (0.47–0.97)	0.035	0.583
		Recessive	G/G-G/A	247 (94.64%)	225 (88.93%)	1			223 (90.28%)	220 (91.29%)	1
			A/A	14 (5.36%)	28 (11.07%)	0.41 (0.21–0.82)	0.011	0.275	24 (9.72%)	21 (8.71%)	1.16 (0.62–2.17)	0.641	0.971
		Log-additive	–	–	–	0.92 (0.69–1.22)	0.558	0.797	–	–	0.82 (0.62–1.08)	0.156	0.520
	rs3218977	Allele	A	396 (75.86%)	382 (75.49%)	1			359 (72.67%)	375 (77.80%)	1
			G	126 (24.14%)	124 (24.51%)	0.98 (0.74–1.30)	0.891	0.891	135 (27.33%)	107 (22.20%)	1.32 (0.98–1.77)	0.064	0.320
		Codominant	A/A	145 (55.56%)	150 (59.29%)	1			126 (51.01%)	140 (58.09%)	1
			A/G	106 (40.61%)	82 (32.41%)	1.37 (0.94–2.00)	0.104	0.400	107 (43.32%)	95 (39.42%)	1.00 (0.90–1.90)	0.155	0.554
			G/G	10 (3.83%)	21 (8.30%)	0.45 (0.20–1.01)	0.052	0.371	14 (5.67%)	6 (2.49%)	2.44 (0.90–6.63)	0.081	0.506
		Dominant	A/A	145 (55.56%)	150 (59.29%)	1			126 (51.01%)	140 (58.09%)	1
			A/G-G/G	116 (44.44%)	103 (40.71%)	1.17 (0.82–1.68)	0.383	0.709	121 (48.99%)	101 (41.91%)	1.38 (0.96–1.98)	0.081	0.579
		Recessive	A/G-A/A	251 (96.17%)	232 (91.70%)	1			233 (94.33%)	235 (97.51%)	1
			G/G	10 (3.83%)	21 (8.30%)	0.40 (0.18–0.88)	0.023	0.383	14 (5.67%)	6 (2.49%)	2.18 (0.81–5.84)	0.123	0.559
		Log-additive	–	–	–	0.97 (0.73–1.30)	0.843	0.878	–	–	1.39 (1.01–1.91)	0.041	0.513
	rs719250	Allele	C	373 (72.29%)	359 (70.95%)	1			376 (76.11%)	337 (69.92%)	1
			T	143 (27.71%)	147 (29.05%)	0.94 (0.71–1.23)	0.635	0.907	118 (23.89%)	145 (30.08%)	0.73 (0.55–0.97)	0.029	0.290
		Codominant	C/C	132 (51.16%)	129 (50.99%)	1			147 (59.51%)	121 (50.21%)	1
			C/T	109 (42.25%)	101 (39.92%)	1.11 (0.76–1.61)	0.589	0.818	82 (33.20%)	95 (39.42%)	0.68 (0.46–1.01)	0.054	0.540
			T/T	17 (6.59%)	23 (9.09%)	0.89 (0.45–1.77)	0.739	0.821	18 (7.29%)	25 (10.37%)	0.54 (0.28–1.05)	0.070	0.583
		Dominant	C/C	132 (51.16%)	129 (50.99%)	1			147 (59.51%)	121 (50.21%)	1
			C/T-T/T	126 (48.84%)	124 (49.01%)	1.07 (0.75–1.53)	0.709	0.865	100 (40.49%)	120 (49.79%)	0.65 (0.45–0.94)	0.022	0.550
		Recessive	C/T-C/C	241 (93.41%)	230 (90.91%)	1			229 (92.71%)	216 (89.63%)	1
			T/T	17 (6.59%)	23 (9.09%)	0.85 (0.44–1.66)	0.633	0.812	18 (7.29%)	25 (10.37%)	0.63 (0.33–1.20)	0.162	0.506
		Log-additive	–	–	–	1.01 (0.76–1.34)	0.927	0.946	–	–	0.71 (0.54–0.95)	0.019	0.937
	rs3218896	Allele	T	447 (85.63%)	429 (85.12%)	1			444 (89.88%)	422 (87.55%)	1
			C	75 (14.37%)	75 (14.88%)	0.96 (0.68–1.36)	0.816	0.907	50 (10.12%)	60 (12.45%)	0.79 (0.53–1.18)	0.251	0.418
		Codominant	T/T	194 (74.33%)	184 (73.02%)	1			202 (81.78%)	185 (76.76%)	1
			T/C	59 (22.61%)	61 (24.21%)	0.95 (0.62–1.45)	0.813	0.884	40 (16.19%)	52 (21.58%)	0.68 (0.43–1.08)	0.105	0.583
			C/C	8 (3.07%)	7 (2.78%)	1.46 (0.51–4.19)	0.478	0.771	5 (2.02%)	4 (1.66%)	0.80 (0.20–3.17)	0.747	0.934
		Dominant	T/T	194 (74.33%)	184 (73.02%)	1			202 (81.78%)	185 (76.76%)	1
			C/T-C/C	67 (25.67%)	68 (26.98%)	1.00 (0.67–1.49)	0.990	0.990	45 (18.22%)	56 (23.24%)	0.69 (0.44–1.08)	0.105	0.525
		Recessive	C/T-T/T	253 (96.93%)	245 (97.22%)	1			242 (97.98%)	237 (98.34%)	1
			C/C	8 (3.07%)	7 (2.78%)	1.48 (0.52–4.22)	0.462	0.770	5 (2.02%)	4 (1.66%)	0.86 (0.22–3.42)	0.835	0.928
		Log-additive	–	–	–	1.04 (0.74–1.47)	0.817	0.869	–	–	0.74 (0.50–1.10)	0.134	0.558
	rs2072472	Allele	A	404 (77.39%)	407 (80.43%)	1			378 (76.52%)	386 (80.08%)	1
			G	118 (22.61%)	99 (19.57%)	1.20 (0.89–1.62)	0.232	0.773	116 (23.48%)	96 (19.92%)	1.23 (0.91–1.68)	0.177	0.443
		Codominant	A/A	150 (57.47%)	168 (66.40%)	1			146 (59.11%)	155 (64.32%)	1
			A/G	104 (39.85%)	71 (28.06%)	1.67 (1.14–2.45)	0.009	0.450	86 (34.82%)	76 (31.54%)	1.18 (0.80–1.74)	0.391	0.752
			G/G	7 (2.68%)	14 (5.53%)	0.51 (0.20–1.32)	0.163	0.408	15 (6.07%)	10 (4.15%)	1.77 (0.76–4.09)	0.185	0.544
		Dominant	A/A	150 (57.47%)	168 66.40%)	1			146 (59.11%)	155 (64.32%)	1
			A/G-G/G	111 (42.53%)	85 (33.60%)	1.47 (1.02–2.12)	0.039	0.390	101 (40.89%)	86 (35.68%)	1.25 (0.86–1.81)	0.238	0.595
		Recessive	A/G-A/A	254 (97.32%)	239 (94.47%)	1			232 (93.93%)	231 (95.85%)	1
			G/G	7 (2.68%)	14 (5.53%)	0.42 (0.16–1.09)	0.075	0.375	15 (6.07%)	10 (4.15%)	1.67 (0.73–3.82)	0.228	0.633
		Log-additive	–	–	–	1.20 (0.88–1.63)	0.262	0.546	–	–	1.25 (0.92–1.69)	0.155	0.554

Notes: OR (95% CI): Calculated by unconditional logistic regression adjusted by gender and age. p - value was calculated by two -sided χ² test. Bold means statistical significance.

Abbreviations: RA, rheumatoid arthritis; IL1R1, interleukin-1 receptor 1; IL1R2, interleukin-1 receptor 2; SNP, single-nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval; FDR, false discovery rate; freq, frequency.

Table 6 The Haplotype Analysis Result of IL1R1/ IL1R2 Polymorphisms and Their Associations with Rheumatoid Arthritis Risk

Gene	SNP	Haplotype	Frequency		Without Adjusted		Adjusted		FDR Test
			RA Patients	Control	OR (95% CI)	p	OR (95% CI)	p
IL1R2	rs3218977| rs2072472	AG	0.77	0.80	0.82 (0.66–1.02)	0.073	0.82 (0.66–1.02)	0.073	0.110
IL1R2	rs3218977| rs2072472	GA	0.26	0.23	1.14 (0.93–1.41)	0.218	1.14 (0.92–1.40)	0.225	0.225
IL1R2	rs3218977| rs2072472	AA	0.51	0.57	0.79 (0.65–0.94)	0.010	0.79 (0.65–0.94)	0.010	0.030

Notes: p- value was calculated by Wald test with and without adjusted by age and gender. Bold means statistical significance.

Abbreviations: RA, rheumatoid arthritis; IL1R2, interleukin-1 receptor 2; SNP, single-nucleotide polymorphism; OR, odds ratio; 95% CI, % confidence interval; FDR, false discovery rate, freq, frequency.

Figure 1 The LD status (r²) of six SNPs of IL-1R2. The number in the diamonds is the LOD score of r². The LD value is determined by r² > 0.8 analyzed by Haploview software 4.2. LD haplotype analysis provides the basis for the selection of sites for association analysis.