Role of IL-17 gene polymorphisms in osteoarthritis: A meta-analysis based on observational studies

Table 1 Characteristics of included studies

Ref.	Yr	Nationality	Osteoarthritis type	Sample size (female / male)		Age (mean)		Study single nucleotide polymorphisms	Genotype method	Newcastle-Ottawa Scale			Hardy-Weinberg equilibrium
				Case	Control	Case	Control			I	II	III
Zhang et al[20]	2019	China	Knee	122 (90/32)	124 (88/36)	66	66	rs2275913	PCR	3	0	3	Yes
								rs763780	PCR	3	0	3	Yes
Zhang et al[20]	2019	China	Knee	76 (52/24)	68 (49/19)	62	61	rs2275913	PCR	3	0	3	Yes
								rs763780	PCR	3	0	3	Yes
Jiang et al[21]	2019	China	NA	410 (271/139)	507 (348/159)	57.35	57.88	rs2275913	PCR-RFLP	3	1	3	Yes
								rs763780	PCR-RFLP	3	1	3	Yes
Bai et al[22]	2019	China	Knee	594 (393/201)	576 (402/174)	59.5	58.3	rs2275913	PCR	3	1	3	Yes
								rs763780	PCR	3	1	3	Yes
Bafrani et al[12]	2019	Iran	Knee	127 (69/58)	127 (73/54)	68.06	66.84	rs2275913	PCR-RFLP	3	1	3	Yes
								rs763780	PCR-RFLP	3	1	3	Yes
								rs2397084	PCR-RFLP	3	1	3	Yes
Vrgoc et al[23]	2018	Croatia	Hip	260 (175/85)	597 (152/445)	67.82	42.64	rs2275913	TaqMan	3	1	3	Yes
								rs763780	TaqMan	3	1	3	Yes
								rs1889570	TaqMan	3	1	3	Yes
Vrgoc et al[23]	2018	Croatia	Knee	240 (174/66)	597 (152/445)	69.74	42.64	rs2275913	TaqMan	3	1	3	Yes
								rs763780	TaqMan	3	1	3	Yes
								rs1889570	TaqMan	3	1	3	Yes
Han et al[24]	2014	SouthKorea	Knee	302 (245/57)	300 (136/164)	60	51	rs2275913	PCR-SSCP	3	0	3	No
								rs763780	PCR-SSCP	3	0	3	No

Newcastle-Ottawa Scale is available from http://www.ohri.ca/programs/clinical epidemiology/oxford.asp. I: Selection; II: Comparability; III: Exposure; NA: Not available; PCR: Polymerase chain reaction; RFLP: Restriction fragment length polymorphism; SSCP: Single-strand conformation polymorphism.

Table 2 Genotype distributions of IL-17 gene polymorphisms in the included studies

Ref.	Source of control	Ethnicity	Allele		Case			Control			Association with osteoarthritis
			1	0	11	10	00	11	10	00
rs2275913
Zhang et al[20], 2019	HB	Asian	G	A	42	53	27	49	63	12	AA genotype/A allele increased OA risk
Zhang et al[20], 2019	HB	Asian			23	32	21	26	28	14	Not related
Jiang et al[21], 2019	HB	Asian			204	170	34	289	194	23	AA genotype/A allele increased OA risk
Bai et al[22], 2019	HB	Asian			189	271	134	207	265	104	AA genotype/A allele increased OA risk
Bafrani et al[12], 2019	HB	Caucasians			83	35	9	69	51	7	GA genotype decreased OA risk
Vrgoc et al[23], 2018	HB	Caucasians			78	71	23	190	172	45	Not related
Vrgoc et al[23], 2018	HB	Caucasians			76	85	25	190	172	45	Not related
Han et al[24], 2014	HB	Asian			52	109	141	97	106	97	GG genotype decreased OA risk
rs763780
Zhang et al[20], 2019	HB	Asian	T	C	91	30	1	98	24	2	Not related
Zhang et al[20], 2019	HB	Asian			59	16	1	54	13	1	Not related
Jiang et al[21], 2019	HB	Asian			356	49	4	423	80	2	Not related
Bai et al[22], 2019	HB	Asian			380	188	26	411	155	10	CC/TC genotype/C allele increased OA risk
Bafrani et al[12], 2019	HB	Caucasians			98	26	3	112	13	2	TC genotype/C allele increased OA risk
Vrgoc et al[23], 2018	HB	Caucasians			198	34	0	493	34	1	C allele increased OA risk
Vrgoc et al[23], 2018	HB	Caucasians			195	14	1	493	34	1	Not related
Han et al[24], 2014	HB	Asian			226	59	17	236	56	8	Not related
rs2397084
Bafrani et al[12], 2019	HB	Caucasians	T	C	111	16	0	109	18	0	Not related
rs1889570
Vrgoc et al[23], 2018	HB	Caucasians	G	A	57	129	58	49	91	46	Not related
Vrgoc et al[23], 2018	HB	Caucasians			68	111	51	49	91	46	Not related

HB: Hospital-based; OA: Osteoarthritis.

Table 3 Meta-analysis of the association between IL-17 gene polymorphisms and osteoarthritis risk

SNP	Comparison	Category	Category	Studies	Odds ratio (95% confidence interval)	P value	I2
rs2275913	A vs G	Total (random model)		8	1.26 (1.08, 1.47)	0.003	61.6%
	Allele model	Ethnicity	Asian	5	1.40 (1.18, 1.67)	< 0.001	56.1%
			Caucasian	3	1.05 (0.84, 1.31)	0.680	38.8%
		OA type	Knee	6	1.28 (1.04, 1.59)	0.023	69.9%
			Hip	1	1.09 (0.83, 1.42)	0.545	-
	AA + GA vs GG	Total (random model)		8	1.25 (1.01, 1.55)	0.039	61.0%
	Dominant model	Ethnicity	Asian	5	1.44 (1.13, 1.82)	0.003	51.4%
			Caucasian	3	0.98 (0.68, 1.41)	0.926	59.8%
		OA type	Knee	6	1.27 (0.93, 1.73)	0.130	70.2%
			Hip	1	1.06 (0.74, 1.51)	0.769	-
	AA vs GA + GG	Total (fixed model)		8	1.53 (1.30, 1.81)	< 0.001	0.0%
	Recessive model	Ethnicity	Asian	5	1.62 (1.34, 1.96)	< 0.001	13.3%
			Caucasian	3	1.25 (0.88, 1.78)	0.209	0.0%
		OA type	Knee	6	1.53 (1.27, 1.84)	< 0.001	0.0%
			Hip	1	1.24 (0.73, 2.13)	0.430	-
	AA vs GG	Total (fixed model)		8	1.71 (1.42, 2.06)	< 0.001	30.2%
	Homozygote model	Ethnicity	Asian	5	1.89 (1.52, 2.34)	< 0.001	40.8%
			Caucasian	3	1.28 (0.88, 1.86)	0.192	0.0%
		OA type	Knee	6	1.74 (1.41, 2.15)	< 0.001	39.8%
			Hip	1	1.25 (0.71, 2.20)	0.449	-
	GA vs GG	Total (fixed model)		8	1.15 (1.01, 1.32)	0.034	47.7%
	Heterozygote model	Ethnicity	Asian	5	1.25 (1.06, 1.46)	0.007	23.7%
			Caucasian	3	0.98 (0.77, 1.24)	0.846	63.1%
		OA type	Knee	6	1.15 (0.98, 1.36)	0.090	60.3%
			Hip	1	1.01 (0.69, 1.47)	0.977	-
rs763780	C vs T	Total (random model)		8	1.32 (1.06,1.64)	0.013	51.5%
	Allele model	Ethnicity	Asian	5	1.19 (0.95, 1.48)	0.132	42.6%
			Caucasian	3	1.75 (1.16, 2.66)	0.008	39.3%
		OA type	Knee	6	1.37 (1.17, 1.60)	< 0.001	0.0%
			Hip	1	2.24 (1.38, 3.63)	0.001	-
	CC + TC vs TT	Total (random model)		8	1.32 (1.02, 1.72)	0.033	58.4%
	Dominant model	Ethnicity	Asian	5	1.15 (0.90, 1.48)	0.274	44.0%
			Caucasian	3	1.82 (1.11, 3.00)	0.018	51.9%
		OA type	Knee	6	1.35 (1.14, 1.61)	0.001	0.0%
			Hip	1	2.42 (1.47, 3.99)	0.001	-
	CC vs TC + TT	Total (fixed model)		8	2.08 (1.30, 3.32)	0.002	0.0%
	Recessive model	Ethnicity	Asian	5	2.17 (1.32, 3.59)	0.002	0.0%
			Caucasian	3	1.48 (0.38, 5.67)	0.570	0.0%
		OA type	Knee	6	2.10 (1.28, 3.45)	0.003	0.0%
			Hip	1	0.76 (0.03, 3.32)	0.864	-
	CC vs TT	Total (fixed model)		8	2.19 (1.37, 3.51)	0.001	0.0%
	Homozygote model	Ethnicity	Asian	5	2.28 (1.37, 3.77)	0.001	0.0%
			Caucasian	3	1.62 (0.42, 6.23)	0.481	0.0%
		OA type	Knee	6	2.23 (1.35, 3.67)	0.002	0.0%
			Hip	1	0.83 (0.03, 20.43)	0.909	-
	TC vs TT	Total (random model)		8	1.29 (0.97, 1.71)	0.078	62.6%
	Heterozygote model	Ethnicity	Asian	5	1.09 (0.85, 1.40)	0.505	40.5%
			Caucasian	3	1.84 (1.06, 3.17)	0.030	57.6%
		OA type	Knee	6	1.28 (1.07, 1.54)	0.008	0.0%
			Hip	1	2.49 (1.51, 4.12)	< 0.001	-

OA: Osteoarthritis; SNP: Single nucleotide polymorphism.

Table 4 False-positive report probability values for associations between IL-17 gene polymorphisms and risk of osteoarthritis

Variables	Odds ratio (95%CI)	P value	Power	Prior probability
				0.25	0.1	0.01	0.001	0.0001
rs2275913
A vs G
All	1.26 (1.08, 1.47)	0.003	0.488	0.018	0.052	0.378	0.860	0.984
Asian	1.40 (1.18, 1.67)	< 0.001	0.673	0.004	0.013	0.128	0.597	0.937
Knee OA	1.28 (1.04, 1.59)	0.023	0.483	0.125	0.300	0.825	0.979	0.998
AA + GA vs GG
All	1.25 (1.01, 1.55)	0.039	0.488	0.194	0.419	0.888	0.988	0.999
Asian	1.44 (1.13, 1.82)	0.003	0.533	0.017	0.048	0.358	0.849	0.983
AA vs GA + GG
All	1.53 (1.30, 1.81)	< 0.001	0.952	0.003	0.009	0.094	0.512	0.913
Asian	1.62 (1.34, 1.96)	< 0.001	0.953	0.003	0.009	0.094	0.512	0.913
Knee OA	1.53 (1.27, 1.84)	< 0.001	0.890	0.003	0.010	0.100	0.529	0.918
AA vs GG
All	1.71 (1.42, 2.06)	< 0.001	0.991	0.003	0.009	0.091	0.502	0.910
Asian	1.89 (1.52, 2.34)	< 0.001	0.995	0.003	0.009	0.091	0.501	0.910
GA vs GG
All	1.15 (1.01, 1.32)	0.034	0.447	0.186	0.406	0.883	0.987	0.999
Asian	1.25 (1.06, 1.46)	0.007	0.548	0.037	0.103	0.559	0.927	0.992
rs763780
C vs T
All	1.32 (1.06,1.64)	0.013	0.509	0.071	0.187	0.717	0.962	0.996
Caucasian	1.75 (1.16, 2.66)	0.008	0.487	0.047	0.129	0.619	0.943	0.994
Knee OA	1.37 (1.17, 1.60)	< 0.001	0.753	0.004	0.012	0.116	0.570	0.930
Hip OA	2.24 (1.38, 3.63)	0.001	0.006	0.018	0.167	0.669	0.953	0.995
CC + TC vs TT
All	1.32 (1.02, 1.72)	0.033	0.470	0.174	0.387	0.874	0.986	0.999
Caucasian	1.82 (1.11, 3.00)	0.018	0.099	0.247	0.783	0.973	0.973	0.997
Knee OA	1.35 (1.14, 1.61)	0.001	0.520	0.006	0.017	0.160	0.658	0.951
Hip OA	2.42 (1.47, 3.99)	0.001	0.569	0.005	0.016	0.148	0.637	0.946
CC vs TC + TT
All	2.08 (1.30, 3.32)	0.002	0.492	0.012	0.035	0.287	0.802	0.976
Caucasian	2.17 (1.32, 3.59)	0.002	0.471	0.013	0.037	0.296	0.809	0.977
Knee OA	2.10 (1.28, 3.45)	0.003	0.485	0.018	0.053	0.380	0.861	0.984
CC vs TT
All	2.19 (1.37, 3.51)	0.001	0.487	0.006	0.018	0.169	0.672	0.954
Caucasian	2.28 (1.37, 3.77)	0.001	0.469	0.006	0.019	0.174	0.681	0.955
Knee OA	2.23 (1.35, 3.67)	0.002	0.526	0.011	0.033	0.274	0.792	0.974
TC vs TT
Caucasian	1.84 (1.06, 3.17)	0.030	0.511	0.150	0.346	0.853	0.983	0.998
Knee OA	1.28 (1.07, 1.54)	0.008	0.486	0.047	0.129	0.620	0.943	0.994
Hip	2.49 (1.51, 1.71)	< 0.001

OA: Osteoarthritis.