突触结合蛋白2基因多态性与中国汉族精神分裂症的关联研究

doi:10.3969/j.issn.1674-8115.2021.01.003

上海交通大学学报(医学版) ›› 2021, Vol. 41 ›› Issue (1): 16-22.doi: 10.3969/j.issn.1674-8115.2021.01.003

突触结合蛋白2基因多态性与中国汉族精神分裂症的关联研究

阳红¹(), 黄欣欣², 刘超³(), 梁青松¹, 杨华¹, 张建标³, 徐健³, 王颖怡², 吴海苏², 吕钦谕²(), 易正辉²

^1.湖南省怀化市第四人民医院临床心理科，怀化 418000
^2.上海交通大学医学院附属精神卫生中心临床六科，上海 201108
^3.江苏省南通市第四人民医院精神二科，南通 226000

出版日期:2021-01-28 发布日期:2021-02-22
通讯作者: 刘超,吕钦谕 E-mail:yanghong2353357@163.com;ntsylc@163.com;lvqinyu_louis@163.com
作者简介:阳红（1977—），女，副主任医师，本科；电子信箱：yanghong2353357@163.com。
基金资助:
国家自然科学基金(81671326);上海市科学技术委员会项目(17411970000);江苏省卫生健康委员会项目(H2018040)

Association study of synaptotagmin 2 gene polymorphisms with schizophrenia in Chinese Han population

Hong YANG¹(), Xin-xin HUANG², Chao LIU³(), Qing-song LIANG¹, Hua YANG¹, Jian-biao ZHANG³, Jian XU³, Ying-yi WANG², Hai-su WU², Qin-yu LÜ²(), Zheng-hui YI²

^1.Department of Clinical Psychology, The Fourth People's Hospital of Huaihua, Hunan Province, Huaihua 418000, China
^2.Sixth Clinical Department, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 201108, China
^3.Second Department of Psychiatry, Nantong Fourth People's Hospital, Jiangsu Province, Nantong 226000, China

Online:2021-01-28 Published:2021-02-22
Contact: Chao LIU,Qin-yu Lü E-mail:yanghong2353357@163.com;ntsylc@163.com;lvqinyu_louis@163.com
Supported by:
Funding Information] National Natural Science Foundation of China(81671326);Shanghai Science and Technology Commission Foundation(17411970000);Project of Jiangsu Provincial Health Committee(H20180400)

摘要/Abstract

摘要：

目的·探讨突触结合蛋白2（synaptotagmin 2，SYT2）基因与中国汉族人群精神分裂症（schizophrenia，SZ）的关联性。方法·采用TaqMan探针基因分型技术对478例SZ患者（SZ组）和474名健康对照者（HC组）的SYT2基因的5个单核苷酸多态性（single nucleotide polymorphism，SNP）位点（rs6427957、rs907697、rs12564274、rs10800856、rs61820945）进行检测分型，应用HaploView软件、SHEsis及SNPstats在线软件比较SZ组与HC组的等位基因、基因型、不同遗传模式下基因型以及单倍型频率分布有无差异。结果·rs10800856位点等位基因及基因型频率分布在SZ组与HC组之间差异有统计学意义（P=0.003，P=0.012）；经Bonferroni 校正后，rs10800856位点等位基因频率差异仍有统计学意义（P=0.015），基因型频率差异无统计学意义。rs10800856位点在显性及加性遗传模式下，基因型频率分布在SZ组与HC组之间比较差异有统计学意义（P=0.004，P=0.005），校正后差异仍有统计学意义（P=0.020，P=0.025）。由rs12564274-rs10800856-rs61820945组成的单倍型C-T-C频率分布在SZ组与HC组间差异有统计学意义（P=0.009）；经Bonferroni校正后，差异仍具有统计学意义（P=0.036）。结论·在中国汉族人群中，SYT2基因可能是SZ的易感基因，rs10800856位点可能与精神分裂症发病风险有关联。

关键词: 精神分裂症, 突触结合蛋白2基因, 单核苷酸多态性, 关联分析

Abstract:

Objective·To investigate the relationship between synaptotagmin 2 (SYT2)gene and schizophrenia (SZ) in Chinese Han population.

Methods·TaqMan probe genotyping technique was used to detect 5 single nucleotide polymorphism (SNP) sites (rs6427957,rs907697,rs12564274,rs10800856 and rs61820945) of SYT2 gene in 478 SZ patients (SZ group) and 474 healthy controls (HC group). HaploView software, SHEsis and SNPstats online software were used to compare the alleles, genotypes, genotypes under different genetic models and haplotypes frequency distribution between the SZ group and HC group.

Results·The frequency distribution differences of rs10800856 allele and genotype were statistically significant between the SZ group and HC group, respectively (P=0.003, P=0.012). After Bonferroni correction, the allele frequency difference of rs10800856 site was still statistically significant (P=0.015), while the genotype frequency difference was not statistically significant. Under the dominant and additive genetic mode, the genotype frequency distributions of rs10800856 site were significantly different between the SZ group and HC group (P=0.004, P=0.005). After correction, the differences were still statistically significant (P=0.020, P=0.025). The frequency distribution of haplotype C-T-C, composed of rs12564274-rs10800856-rs61820945, between the SZ group and HC group was significantly different (P=0.009). After Bonferroni correction, the difference was still statistically significant (P=0.036).

Conclusion·In Chinese Han population, SYT2 may be the susceptibility gene of SZ, and rs10800856 site may be associated with the risk of SZ.

Key words: schizophrenia (SZ), synaptotagmin 2 (SYT2) gene, single nucleotide polymorphism (SNP), association analysis

中图分类号:

R749.3

阳红, 黄欣欣, 刘超, 梁青松, 杨华, 张建标, 徐健, 王颖怡, 吴海苏, 吕钦谕, 易正辉. 突触结合蛋白2基因多态性与中国汉族精神分裂症的关联研究[J]. 上海交通大学学报(医学版), 2021, 41(1): 16-22.

Hong YANG, Xin-xin HUANG, Chao LIU, Qing-song LIANG, Hua YANG, Jian-biao ZHANG, Jian XU, Ying-yi WANG, Hai-su WU, Qin-yu LÜ, Zheng-hui YI. Association study of synaptotagmin 2 gene polymorphisms with schizophrenia in Chinese Han population[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(1): 16-22.

SNP	Allele/Genotype		SZ group/n (%)	HC group/n (%)	χ² value	P value (adjusted)	OR (95%CI)
rs10800856^①
	Allele	A	581 (73.7)	742 (79.8)	8.830	0.015	0.711 (0.568?0.891)
		T	207 (26.3)	188 (20.2)
	Genotype	AA	217 (55.1)	302 (64.9)	8.852	0.060
		AT	147 (37.3)	138 (29.7)
		TT	30 (7.6)	25 (5.4)
rs12564274^②
	Allele	C	387 (40.7)	378 (40.3)	0.038	1.000	1.018 (0.847?1.224)
		G	563 (59.3)	560 (59.7)
	Genotype	CC	86 (18.1)	75 (16.0)	1.283	1.000
		CG	215 (45.3)	228 (48.6)
		GG	174 (36.6)	166 (35.4)
rs61820945^③
	Allele	C	716 (75.2)	713 (75.4)	0.007	1.000	0.991 (0.805?1.221)
		G	236 (24.8)	233 (24.6)
	Genotype	CC	271 (56.9)	263 (55.6)	1.764	1.000
		CG	174 (36.6)	187 (39.5)
		GG	31 (6.5)	23 (4.9)
rs6427957^④
	Allele	A	642 (67.6)	639 (68.3)	0.103	1.000	0.969 (0.798?1.176)
		G	308 (32.4)	297 (31.7)
	Genotype	AA	217 (45.7)	222 (47.4)	0.434	1.000
		GA	208 (43.8)	195 (41.7)
		GG	50 (10.5)	51 (10.9)
rs907697^⑤
	Allele	C	326 (34.3)	331 (35.1)	0.141	1.000	0.964 (0.798?1.165)
		T	624 (65.7)	611 (64.9)
	Genotype	CC	60 (12.6)	67 (14.2)	0.580	1.000
		CT	206 (43.4)	197 (41.8)
		TT	209 (44.0)	207 (43.9)

SNP	Allele/Genotype		SZ group/n (%)	HC group/n (%)	χ² value	P value (adjusted)	OR (95%CI)
rs10800856^①
	Allele	A	581 (73.7)	742 (79.8)	8.830	0.015	0.711 (0.568?0.891)
		T	207 (26.3)	188 (20.2)
	Genotype	AA	217 (55.1)	302 (64.9)	8.852	0.060
		AT	147 (37.3)	138 (29.7)
		TT	30 (7.6)	25 (5.4)
rs12564274^②
	Allele	C	387 (40.7)	378 (40.3)	0.038	1.000	1.018 (0.847?1.224)
		G	563 (59.3)	560 (59.7)
	Genotype	CC	86 (18.1)	75 (16.0)	1.283	1.000
		CG	215 (45.3)	228 (48.6)
		GG	174 (36.6)	166 (35.4)
rs61820945^③
	Allele	C	716 (75.2)	713 (75.4)	0.007	1.000	0.991 (0.805?1.221)
		G	236 (24.8)	233 (24.6)
	Genotype	CC	271 (56.9)	263 (55.6)	1.764	1.000
		CG	174 (36.6)	187 (39.5)
		GG	31 (6.5)	23 (4.9)
rs6427957^④
	Allele	A	642 (67.6)	639 (68.3)	0.103	1.000	0.969 (0.798?1.176)
		G	308 (32.4)	297 (31.7)
	Genotype	AA	217 (45.7)	222 (47.4)	0.434	1.000
		GA	208 (43.8)	195 (41.7)
		GG	50 (10.5)	51 (10.9)
rs907697^⑤
	Allele	C	326 (34.3)	331 (35.1)	0.141	1.000	0.964 (0.798?1.165)
		T	624 (65.7)	611 (64.9)
	Genotype	CC	60 (12.6)	67 (14.2)	0.580	1.000
		CT	206 (43.4)	197 (41.8)
		TT	209 (44.0)	207 (43.9)

SNP	Genetic model	Genotype	SZ group/n (%)	HC group/n (%)	P value (adjusted)	OR (95%CI)
rs10800856
	Co-dominant	A/A	215 (55.0)	302 (65.0)	0.075	1.000
		T/A	146 (37.3)	138 (29.7)		1.480 (1.100?1.980)
		T/T	30 (7.7)	25 (5.4)		1.640 (0.930?2.880)
	Dominant	A/A	215 (55.0)	302 (65.0)	0.020	1.000
		T/A+T/T	176 (45.0)	163 (35.0)		1.500 (1.140?1.980)
	Recessive	A/A+T/A	361 (92.3)	440 (94.6)	1.000	1.000
		T/T	30 (7.7)	25 (5.4)		1.430 (0.820?2.480)
	Log-additive	-	-	-	0.026	1.370 (1.100?1.710)
rs12564274
	Co-dominant	G/G	172 (36.4)	166 (35.4)	1.000	1.000
		G/C	215 (45.6)	228 (48.6)		0.900 (0.680?1.200)
		C/C	85 (18.0)	75 (16.0)		1.070 (0.730?1.570)
	Dominant	G/G	172 (36.4)	166 (35.4)	1.000	1.000
		G/C+C/C	300 (63.6)	303 (64.6)		0.940 (0.720?1.230)
	Recessive	G/G+G/C	387 (82.0)	394 (84.0)	1.000	1.000
		C/C	85 (18.0)	75 (16.0)		1.130 (0.800?1.600)
	Log-additive	-	-	-	1.000	1.010 (0.840?1.210)
rs61820945
	Co-dominant	C/C	270 (57.1)	263 (55.6)	1.000	1.000
		G/C	173 (36.6)	187 (39.5)		0.880 (0.670?1.160)
		G/G	30 (6.3)	23 (4.9)		1.170 (0.660?2.100)
	Dominant	C/C	270 (57.1)	263 (55.6)	1.000	1.000
		G/C+G/G	203 (42.9)	210 (44.4)		0.910 (0.700?1.190)
	Recessive	C/C+G/C	443 (93.7)	450 (95.1)	1.000	1.000
		G/G	30 (6.3)	23 (4.9)		1.240 (0.700?2.180)
	Log-additive	-	-	-	1.000	0.970 (0.780?1.200)
rs6427957
	Co-dominant	A/A	216 (45.8)	222 (47.4)	1.000	1.000
		G/A	206 (43.6)	195 (41.7)		1.040 (0.790?1.370)
		G/G	50 (10.6)	51 (10.9)		1.010 (0.650?1.560)
	Dominant	A/A	216 (45.8)	222 (47.4)	1.000	1.000
		G/A+G/G	256 (54.2)	246 (52.6)		1.030 (0.800?1.340)
	Recessive	A/A+G/A	422 (89.4)	417 (89.1)	1.000	1.000
		G/G	50 (10.6)	51 (10.9)		0.990 (0.650?1.500)
	Log-additive	-	-	-	1.000	1.010 (0.840?1.230)
rs907697
	Co-dominant	T/T	206 (43.6)	207 (44.0)	1.000	1.000
		T/C	206 (43.6)	197 (41.8)		1.070 (0.810?1.410)
		C/C	60 (12.7)	67 (14.2)		0.920 (0.610?1.370)
	Dominant	T/T	206 (43.6)	207 (44.0)	1.000	1.000
		T/C+C/C	266 (56.4)	264 (56.0)		1.030 (0.790?1.340)
	Recessive	T/T+T/C	412 (87.3)	404 (85.8)	1.000	1.000
		C/C	60 (12.7)	67 (14.2)		0.890 (0.610?1.300)
	Log-additive	-	-	-	1.000	0.990 (0.820?1.190)

SNP	Genetic model	Genotype	SZ group/n (%)	HC group/n (%)	P value (adjusted)	OR (95%CI)
rs10800856
	Co-dominant	A/A	215 (55.0)	302 (65.0)	0.075	1.000
		T/A	146 (37.3)	138 (29.7)		1.480 (1.100?1.980)
		T/T	30 (7.7)	25 (5.4)		1.640 (0.930?2.880)
	Dominant	A/A	215 (55.0)	302 (65.0)	0.020	1.000
		T/A+T/T	176 (45.0)	163 (35.0)		1.500 (1.140?1.980)
	Recessive	A/A+T/A	361 (92.3)	440 (94.6)	1.000	1.000
		T/T	30 (7.7)	25 (5.4)		1.430 (0.820?2.480)
	Log-additive	-	-	-	0.026	1.370 (1.100?1.710)
rs12564274
	Co-dominant	G/G	172 (36.4)	166 (35.4)	1.000	1.000
		G/C	215 (45.6)	228 (48.6)		0.900 (0.680?1.200)
		C/C	85 (18.0)	75 (16.0)		1.070 (0.730?1.570)
	Dominant	G/G	172 (36.4)	166 (35.4)	1.000	1.000
		G/C+C/C	300 (63.6)	303 (64.6)		0.940 (0.720?1.230)
	Recessive	G/G+G/C	387 (82.0)	394 (84.0)	1.000	1.000
		C/C	85 (18.0)	75 (16.0)		1.130 (0.800?1.600)
	Log-additive	-	-	-	1.000	1.010 (0.840?1.210)
rs61820945
	Co-dominant	C/C	270 (57.1)	263 (55.6)	1.000	1.000
		G/C	173 (36.6)	187 (39.5)		0.880 (0.670?1.160)
		G/G	30 (6.3)	23 (4.9)		1.170 (0.660?2.100)
	Dominant	C/C	270 (57.1)	263 (55.6)	1.000	1.000
		G/C+G/G	203 (42.9)	210 (44.4)		0.910 (0.700?1.190)
	Recessive	C/C+G/C	443 (93.7)	450 (95.1)	1.000	1.000
		G/G	30 (6.3)	23 (4.9)		1.240 (0.700?2.180)
	Log-additive	-	-	-	1.000	0.970 (0.780?1.200)
rs6427957
	Co-dominant	A/A	216 (45.8)	222 (47.4)	1.000	1.000
		G/A	206 (43.6)	195 (41.7)		1.040 (0.790?1.370)
		G/G	50 (10.6)	51 (10.9)		1.010 (0.650?1.560)
	Dominant	A/A	216 (45.8)	222 (47.4)	1.000	1.000
		G/A+G/G	256 (54.2)	246 (52.6)		1.030 (0.800?1.340)
	Recessive	A/A+G/A	422 (89.4)	417 (89.1)	1.000	1.000
		G/G	50 (10.6)	51 (10.9)		0.990 (0.650?1.500)
	Log-additive	-	-	-	1.000	1.010 (0.840?1.230)
rs907697
	Co-dominant	T/T	206 (43.6)	207 (44.0)	1.000	1.000
		T/C	206 (43.6)	197 (41.8)		1.070 (0.810?1.410)
		C/C	60 (12.7)	67 (14.2)		0.920 (0.610?1.370)
	Dominant	T/T	206 (43.6)	207 (44.0)	1.000	1.000
		T/C+C/C	266 (56.4)	264 (56.0)		1.030 (0.790?1.340)
	Recessive	T/T+T/C	412 (87.3)	404 (85.8)	1.000	1.000
		C/C	60 (12.7)	67 (14.2)		0.890 (0.610?1.300)
	Log-additive	-	-	-	1.000	0.990 (0.820?1.190)

Haplotype	SZ group/n (%)	HC group/n (%)	χ² value	P value	OR (95%CI)
A-C	308.70 (32.6)	324.18 (34.7)	0.666	0.414	0.923 (0.762－1.118)
A-T	332.30 (35.1)	312.82 (33.5)	0.791	0.374	1.091 (0.901－1.320)
G-T	290.70 (30.7)	291.18 (31.2)	0.006	0.936	0.992 (0.815－1.207)

突触结合蛋白2基因多态性与中国汉族精神分裂症的关联研究

Association study of synaptotagmin 2 gene polymorphisms with schizophrenia in Chinese Han population

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Metrics

Haplotype	SZ group/n (%)	HC group/n (%)	χ² value	P value (adjusted)	OR (95%CI)
C-A-C	132.36 (16.8)	192.19 (20.8)	3.825	1.000	0.783 (0.612－1.001)
C-T-C	191.64 (24.4)	179.80 (19.5)	6.799	0.036	1.359 (1.079－1.711)
G-A-C	254.34 (32.4)	319.82 (34.6)	0.633	1.000	0.921 (0.752－1.128)
G-A-G	192.30 (24.5)	225.99 (24.5)	0.024	1.000	1.180 (0.815－1.271)

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