Association between genetic polymorphisms of MMPs and the risk of non-traumaticosteonecrosis of the femoral head in the Han population of northern China

doi:10.3877/cma.j.issn.2096-0263.2019.02.002

Abstract

Abstract:

Objective

The aim of this study was to identify the associations between genes selected from MMPs/TIMPs system and the risk of NONFH, which can provide the genetic basis for the early diagnosis and prevention.

Methods

In the case-control study, we recruited 585 patients who were diagnosed with NONFH and 507 controls. Peripheral blood DNA was extracted, respectively. We genotyped 42 SNPs chosen from 9 genes of MMPs by Sequenom Mass ARRAY. The chi-square test and SNPStats analysis software were used to make statistical analysis and evaluate the association between SNPs and NONFH.

Results

TheMMP8 rs11225394 SNP, the MMP3 rs522616 SNP were associated with an increased risk of NONFH. The MMP3 rs650108 SNP, the MMP9 rs2274755 SNP were associated with a decreased risk of NONFH. In addition, the haplotype "TGC" and the haplotype "CTC" of MMP9 were found to be more likely to decrease the risk of the NONFH than the wild haplotype.

Conclusion

The genetic polymorphisms of MMP3, MMP8, MMP9 are related to the risk of non-traumaticosteonecrosis of femoral head in the Han population of northern China.

Key words: Femur head necrosis, Polymorphism, single-nucleotide, Matrix metalloproteinases, Association study

Feimeng An, Yuju Cao, Jianzhong Wang. Association between genetic polymorphisms of MMPs and the risk of non-traumaticosteonecrosis of the femoral head in the Han population of northern China[J]. Chinese Journal of Geriatric Orthopaedics and Rehabilitation(Electronic Edition), 2019, 05(02): 68-74.

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Figures/Tables 5

References 31

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组别	例数	性别[例（%）]		年龄（岁，±s）
组别	例数	男性	女性	年龄（岁，±s）
病例组	585	472（80.7）	396（78.1）	43±13
对照组	507	113（19.3）	111（21.9）	47±10
统计值		χ²=1.110		t=7.010
P值		0.293		<0.001

组别	例数	性别[例（%）]		年龄（岁，±s）
组别	例数	男性	女性	年龄（岁，±s）
病例组	585	472（80.7）	396（78.1）	43±13
对照组	507	113（19.3）	111（21.9）	47±10
统计值		χ²=1.110		t=7.010
P值		0.293		<0.001

SNP	基因	位置	等位基因（A/B）	MAF		HWE P^a值	OR值	95% CI		P^b值
SNP	基因	位置	等位基因（A/B）	病例组对照组		HWE P^a值	OR值	下限	上限	P^b值
rs14983	MMP7	11q22.2	A/G	0.261	0.264	0.820	0.98	0.81	1.19	0.848
rs17352054	MMP7	11q22.2	C/A	0.121	0.122	0.679	0.99	0.77	1.28	0.948
rs10502001	MMP7	11q22.2	T/C	0.262	0.264	0.820	0.99	0.82	1.20	0.939
rs11568818	MMP7	11q22.2	C/T	0.096	0.090	0.584	1.07	0.80	1.44	0.631
rs17098318	MMP7	11q22.2	A/G	0.094	0.087	0.569	1.09	0.81	1.47	0.557
rs3740938	MMP8	11q22.2	A/G	0.243	0.235	0.621	1.04	0.86	1.27	0.680
rs2012390	MMP8	11q22.2	G/A	0.276	0.276	0.912	1.00	0.83	1.20	0.981
rs1940475	MMP8	11q22.2	T/C	0.387	0.369	0.775	1.08	0.91	1.29	0.378
rs11225394	MMP8	11q22.2	T/C	0.112	0.086	0.563	1.34	1.00	1.79	0.047^*
rs11225395	MMP8	11q22.2	A/G	0.379	0.360	0.773	1.08	0.91	1.29	0.367
rs5854	MMP1	11q22.2	A/G	0.095	0.090	0.165	1.06	0.80	1.42	0.680
rs2071230	MMP1	11q22.2	G/A	0.186	0.190	0.042^#	0.97	0.79	1.21	0.811
rs2239008	MMP1	11q22.2	G/A	0.491	0.480	0.929	1.05	0.88	1.24	0.602
rs470215	MMP1	11q22.2	C/T	0.095	0.090	0.165	1.06	0.80	1.42	0.680
rs2071232	MMP1	11q22.2	T/C	0.483	0.470	0.594	1.05	0.89	1.24	0.560
rs639752	MMP3	11q22.2	C/A	0.318	0.345	0.116	0.88	0.74	1.06	0.177
rs650108	MMP3	11q22.2	G/A	0.391	0.435	0.147	0.84	0.71	0.99	0.040^*
rs520540	MMP3	11q22.2	A/G	0.318	0.345	0.116	0.88	0.74	1.06	0.177
rs646910	MMP3	11q22.2	A/T	0.072	0.086	1.000	0.82	0.60	1.13	0.224
rs602128	MMP3	11q22.2	A/G	0.320	0.344	0.235	0.90	0.75	1.07	0.234
rs679620	MMP3	11q22.2	T/C	0.318	0.347	0.202	0.88	0.74	1.05	0.156
rs678815	MMP3	11q22.2	G/C	0.319	0.347	0.141	0.88	0.74	1.05	0.165
rs522616	MMP3	11q22.2	C/T	0.396	0.354	0.923	1.20	1.01	1.42	0.044^*
rs1053605	MMP2	16q12.2	T/C	0.112	0.129	0.843	0.85	0.66	1.10	0.217
rs243849	MMP2	16q12.2	T/C	0.191	0.167	1.000	1.18	0.95	1.47	0.146
rs243847	MMP2	16q12.2	C/T	0.415	0.405	0.117	1.04	0.88	1.24	0.634
rs243832	MMP2	16q12.2	C/G	0.362	0.382	0.347	0.92	0.77	1.10	0.353
rs7201	MMP2	16q12.2	C/A	0.245	0.255	0.349	0.95	0.78	1.15	0.603
rs2277698	TIMP2	17q25.3	T/C	0.202	0.203	1.000	0.99	0.81	1.22	0.942
rs2009196	TIMP2	17q25.3	C/G	0.394	0.384	0.452	1.04	0.88	1.24	0.646
rs7342880	TIMP2	17q25.3	A/C	0.166	0.148	0.725	1.14	0.91	1.44	0.253
rs11654470	TIMP2	17q25.3	C/T	0.228	0.238	1.000	0.95	0.78	1.16	0.601
rs2003241	TIMP2	17q25.3	C/T	0.161	0.163	0.414	0.99	0.78	1.24	0.897
rs4789936	TIMP2	17q25.3	T/C	0.250	0.281	0.913	0.85	0.71	1.04	0.111
rs3918249	MMP9	20q13.12	T/C	0.297	0.322	0.613	0.89	0.74	1.06	0.191
rs2274755	MMP9	20q13.12	T/G	0.116	0.151	0.729	0.74	0.58	0.95	0.017^*
rs3918254	MMP9	20q13.12	T/C	0.203	0.187	0.664	1.10	0.89	1.36	0.372
rs9619311	SYN3	22q12.3	C/T	0.083	0.068	0.720	1.24	0.90	1.71	0.188
rs715572	TIMP3	22q12.3	A/G	0.342	0.339	0.921	1.01	0.85	1.21	0.897
rs8136803	TIMP3	22q12.3	T/G	0.041	0.049	1.000	0.82	0.55	1.24	0.351
rs9609643	TIMP3	22q12.3	A/G	0.138	0.131	0.696	1.06	0.83	1.35	0.660
rs11547635	TIMP3	22q12.3	T/C	0.344	0.349	1.000	0.98	0.82	1.17	0.819

SNP	基因	位置	等位基因（A/B）	MAF		HWE P^a值	OR值	95% CI		P^b值
SNP	基因	位置	等位基因（A/B）	病例组对照组		HWE P^a值	OR值	下限	上限	P^b值
rs14983	MMP7	11q22.2	A/G	0.261	0.264	0.820	0.98	0.81	1.19	0.848
rs17352054	MMP7	11q22.2	C/A	0.121	0.122	0.679	0.99	0.77	1.28	0.948
rs10502001	MMP7	11q22.2	T/C	0.262	0.264	0.820	0.99	0.82	1.20	0.939
rs11568818	MMP7	11q22.2	C/T	0.096	0.090	0.584	1.07	0.80	1.44	0.631
rs17098318	MMP7	11q22.2	A/G	0.094	0.087	0.569	1.09	0.81	1.47	0.557
rs3740938	MMP8	11q22.2	A/G	0.243	0.235	0.621	1.04	0.86	1.27	0.680
rs2012390	MMP8	11q22.2	G/A	0.276	0.276	0.912	1.00	0.83	1.20	0.981
rs1940475	MMP8	11q22.2	T/C	0.387	0.369	0.775	1.08	0.91	1.29	0.378
rs11225394	MMP8	11q22.2	T/C	0.112	0.086	0.563	1.34	1.00	1.79	0.047^*
rs11225395	MMP8	11q22.2	A/G	0.379	0.360	0.773	1.08	0.91	1.29	0.367
rs5854	MMP1	11q22.2	A/G	0.095	0.090	0.165	1.06	0.80	1.42	0.680
rs2071230	MMP1	11q22.2	G/A	0.186	0.190	0.042^#	0.97	0.79	1.21	0.811
rs2239008	MMP1	11q22.2	G/A	0.491	0.480	0.929	1.05	0.88	1.24	0.602
rs470215	MMP1	11q22.2	C/T	0.095	0.090	0.165	1.06	0.80	1.42	0.680
rs2071232	MMP1	11q22.2	T/C	0.483	0.470	0.594	1.05	0.89	1.24	0.560
rs639752	MMP3	11q22.2	C/A	0.318	0.345	0.116	0.88	0.74	1.06	0.177
rs650108	MMP3	11q22.2	G/A	0.391	0.435	0.147	0.84	0.71	0.99	0.040^*
rs520540	MMP3	11q22.2	A/G	0.318	0.345	0.116	0.88	0.74	1.06	0.177
rs646910	MMP3	11q22.2	A/T	0.072	0.086	1.000	0.82	0.60	1.13	0.224
rs602128	MMP3	11q22.2	A/G	0.320	0.344	0.235	0.90	0.75	1.07	0.234
rs679620	MMP3	11q22.2	T/C	0.318	0.347	0.202	0.88	0.74	1.05	0.156
rs678815	MMP3	11q22.2	G/C	0.319	0.347	0.141	0.88	0.74	1.05	0.165
rs522616	MMP3	11q22.2	C/T	0.396	0.354	0.923	1.20	1.01	1.42	0.044^*
rs1053605	MMP2	16q12.2	T/C	0.112	0.129	0.843	0.85	0.66	1.10	0.217
rs243849	MMP2	16q12.2	T/C	0.191	0.167	1.000	1.18	0.95	1.47	0.146
rs243847	MMP2	16q12.2	C/T	0.415	0.405	0.117	1.04	0.88	1.24	0.634
rs243832	MMP2	16q12.2	C/G	0.362	0.382	0.347	0.92	0.77	1.10	0.353
rs7201	MMP2	16q12.2	C/A	0.245	0.255	0.349	0.95	0.78	1.15	0.603
rs2277698	TIMP2	17q25.3	T/C	0.202	0.203	1.000	0.99	0.81	1.22	0.942
rs2009196	TIMP2	17q25.3	C/G	0.394	0.384	0.452	1.04	0.88	1.24	0.646
rs7342880	TIMP2	17q25.3	A/C	0.166	0.148	0.725	1.14	0.91	1.44	0.253
rs11654470	TIMP2	17q25.3	C/T	0.228	0.238	1.000	0.95	0.78	1.16	0.601
rs2003241	TIMP2	17q25.3	C/T	0.161	0.163	0.414	0.99	0.78	1.24	0.897
rs4789936	TIMP2	17q25.3	T/C	0.250	0.281	0.913	0.85	0.71	1.04	0.111
rs3918249	MMP9	20q13.12	T/C	0.297	0.322	0.613	0.89	0.74	1.06	0.191
rs2274755	MMP9	20q13.12	T/G	0.116	0.151	0.729	0.74	0.58	0.95	0.017^*
rs3918254	MMP9	20q13.12	T/C	0.203	0.187	0.664	1.10	0.89	1.36	0.372
rs9619311	SYN3	22q12.3	C/T	0.083	0.068	0.720	1.24	0.90	1.71	0.188
rs715572	TIMP3	22q12.3	A/G	0.342	0.339	0.921	1.01	0.85	1.21	0.897
rs8136803	TIMP3	22q12.3	T/G	0.041	0.049	1.000	0.82	0.55	1.24	0.351
rs9609643	TIMP3	22q12.3	A/G	0.138	0.131	0.696	1.06	0.83	1.35	0.660
rs11547635	TIMP3	22q12.3	T/C	0.344	0.349	1.000	0.98	0.82	1.17	0.819

SNP	模型	基因型	对照组	病例组	调整后		AIC	BIC
SNP	模型	基因型	对照组	病例组	OR（95% CI）	P^a值	AIC	BIC
rs11225394	共显性	C/C	405（83.2%）	456（78.1%）	1	0.073	1437.9	1462.8
		T/C	80（16.4%）	125（21.4%）	1.44（1.05-1.98）
		T/T	2（0.4%）	3（0.5%）	1.14（0.18-7.08）
	显性	C/C	405（83.2%）	456（78.1%）	1	0.023*	1435.9	1455.9
		T/C-T/T	82（16.8%）	128（21.9%）	1.44（1.05-1.96）
	隐性	C/C-T/C	485（99.6%）	581（99.5%）	1	0.950	1441.1	1461
		T/T	2（0.4%）	3（0.5%）	1.07（0.17-6.61）
	加性	---	---	---	1.40（1.04-1.90）	0.027*	1436.3	1456.2
rs650108	共显性	A/A	153（30.3%）	216（37%）	1	0.058	1461.8	1486.8
		A/G	265（52.5%）	279（47.8%）	0.73（0.55-0.96）
		G/G	87（17.2%）	89（15.2%）	0.74（0.51-1.07）
	显性	A/A	153（30.3%）	216（37%）	1	0.017*	1459.8	1479.8
		A/G-G/G	352（69.7%）	368（63%）	0.73（0.56-0.95）
	隐性	A/A-A/G	418（82.8%）	495（84.8%）	1	0.500	1465	1485
		G/G	87（17.2%）	89（15.2%）	0.89（0.64-1.24）
	加性	---	---	---	0.83（0.70-1.00）	0.044*	1461.5	1481.4
rs522616	共显性	T/T	212（41.9%）	224（38.3%）	1	0.052	1464.3	1489.2
		T/C	230（45.5%）	259（44.3%）	1.08（0.83-1.40）
		C/C	64（12.7%）	102（17.4%）	1.57（1.08-2.29）
	显性	T/T	212（41.9%）	224（38.3%）	1	0.190	1466.4	1486.4
		T/C-C/C	294（58.1%）	361（61.7%）	1.18（0.92-1.52）
	隐性	T/T-T/C	442（87.3%）	483（82.6%）	1	0.018*	1462.6	1482.5
		C/C	64（12.7%）	102（17.4%）	1.52（1.07-2.14）
	加性	---	---	---	1.21（1.02-1.44）	0.033*	1463.6	1483.6
rs2274755	共显性	G/G	364（71.8%）	457（78.1%）	1	0.040*	1508.4	1523.4
		G/T	133（26.2%）	120（20.5%）	0.70（0.52-0.93）
		T/T	10（2%）	8（1.4%）	0.65（0.25-1.68）
	显性	G/G	364（71.8%）	457（78.1%）	1	0.011*	1506.4	1516.4
		G/T-T/T	143（28.2%）	128（21.9%）	0.70（0.52-0.92）
	隐性	G/G-G/T	497（98%）	577（98.6%）	1	0.470	1511.6	1521.6
		T/T	10（2%）	8（1.4%）	0.70（0.27-1.83）
	加性	---	---	---	0.72（0.56-0.94）	0.013*	1506.5	1516.5

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