中国西部汉族人群血小板源性生长因子C基因单核苷酸多态性与非综合征型唇腭裂相关性研究

doi:10.7518/hxkq.2020.04.002

摘要/Abstract

摘要：

目的探究中国西部汉族人群血小板源性生长因子C（PDGF-C）基因的靶向单核苷酸多态性（SNPs）位点rs4691383、rs7667857及其基因型以及环境暴露因素与非综合征型唇腭裂（NSCL/P）发生的相关性。方法收集268个NSCL/P病例—父母核心三人家系,采用聚合酶链反应—限制性酶切片段长度多态法和直接测序法对2个靶向SNPs位点（rs4691383、rs7667857）进行基因分型,使用哈温平衡检验、连锁不平衡检验、传递不平衡检验、单倍型关联分析等方法进行统计学分析。同时收集纳入对象所填写的唇腭裂流行病学研究问卷,对PDGF-C基因和环境暴露因素之间是否存在交互作用进行条件Logistic回归分析。结果 PDGF-C基因rs4691383位点的A等位基因和rs7667857位点的G等位基因在NSCL/P发生中存在过度传递（P<0.05）。孕妇吸烟/被动吸烟史、叶酸补充史、环境有害气体长期吸入史3个环境暴露因素与PDGF-C基因的SNPs位点基因型之间均不存在交互作用（P>0.05）。结论 PDGF-C基因rs4691383位点和rs7667857位点多态性与中国西部汉族人群NSCL/P的发生具有相关性;但在NSCL/P的发生过程中环境暴露因素与PDGF-C基因的SNPs位点基因型之间的交互作用不明显。

关键词: 非综合征型唇腭裂, 血小板源性生长因子C, 单核苷酸多态性, Logistic回归分析

Abstract:

Objective To explore the association between two single nucleotide polymorphisms (SNPs), namely, rs4691383 and rs7667857, in the platelet-derived growth factor-C (PDGF-C) gene, the genotypes, environmental exposure factors, and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Western Chinese population. Methods A total of 268 case—parent trios were selected, and two SNPs (rs4691383 andrs7667857) were genotyped by using polymerase chain reaction and restriction enzyme fragment length polymorphic method and direct sequencing method. Hardy—Weinberg equilibrium, linkage disequilibrium test, transmission disequilibrium test, and haplotype analysis were conducted to analyze the data. Meanwhile, the questionnaires on the epidemiology of cleft lip and palate filled by the included samples were collected, and the interaction between the genotypes of the two SNPs and environmental exposure factors was assessed by conditional logistic regression. Results The A allele at rs4691383 and the G allele at rs7667857 of PDGF-C gene were over-transmitted for NSCL/P (P<0.05). No interaction effect was observed between the three environmental exposure factors (history of smoking/passive smoking, folic acid supplementation, and long-term inhalation of harmful environmental gases) and the PDGF-C genotypes among NSCL/P (P>0.05). Conclusion The rs4691383 and rs7667857 at PDGF-C gene are closely related to the occurrence of NSCL/P in Western Chinese population. However, the interaction between environmental exposure factors and PDGF-C genotypes is not obvious in the occurrence of NSCL/P.

Key words: nonsyndromic cleft lip with or without cleft palate, platelet-derived growth factor-C, single nucleotide polymorphisms, Logistic regression analysis

中图分类号:

R782.2

周玉兰, 朱文超, 石冰, 贾仲林. 中国西部汉族人群血小板源性生长因子C基因单核苷酸多态性与非综合征型唇腭裂相关性研究[J]. 华西口腔医学杂志, 2020, 38(4): 364-370.

Zhou Yulan, Zhu Wenchao, Shi Bing, Jia Zhonglin. Association between platelet-derived growth factor-C single nucleotide polymorphisms and nonsyndromic cleft lip with or without cleft palate in Western Chinese population[J]. West China Journal of Stomatology, 2020, 38(4): 364-370.

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SNPs	等位基因	杂合度
rs4691383	A/G	0.463
rs7667857	G/A	0.273

SNPs	等位基因	引物序列	温度/℃	PCR片段长度/bp
rs7667857	A/G	正义：5’-GGATGGATAGACAGAGGAGTG-3’	61	652
		反义：5’-CTTTTTTCAAGAGACAGGGTT-3’
rs4691383	A/G	正义：5’-GCTTCTTAGGCTCCCATCCAC-3’	56	334
		反义：5’-TTACAAACACGCACCACCACT-3’

SNPs		NSCLP		NSCPO		NSCL/P
SNPs		传递	未传递	传递	未传递	传递	未传递
rs4691383	G	119	186	34	60	153	246
	A	199	132	68	42	267	174
	χ²值	28.280		13.337		41.289
	P值	0.000 0		0.000 0		0.000 0
	OR值	0.424		0.350		0.405
	95%CI	0.309~0.583		0.198~0.619		0.307~0.535
rs4691383	G	164	145	74	40	238	185
	A	130	149	34	68	164	217
	χ²值	2.462		21.474		14.013
	P值	0.117 0		0.000 0		0.000 0
	OR值	1.296		3.700		1.702
	95%CI	0.937~1.793		2.106~6.500		1.287~2.251

单倍型	rs4691383	rs7667857	单倍型频率	P值
1	G	G	0.267	0.283 995
2	A	A	0.257	0.016 504
3	A	G	0.255	0.000 041
4	G	A	0.221	0.000 000

SNPs	吸烟或被动吸烟史	基因型	NSCLP					NSCPO
SNPs	吸烟或被动吸烟史	基因型	频数	OR值	95%CI	LRT	P值	频数	OR值	95%CI	LRT	P值
rs4691383	无吸烟或被动吸烟	AA	19	5.592	1.700~18.389	1 443.88	0.956	5	4.156	0.401~43.119	332.756	0.976
	无吸烟或被动吸烟	GA	30	4.055	1.393~11.807			6	3.117	0.368~27.437
	吸烟或被动吸烟	AA	37	3.866	1.834~8.153			14	5.234	1.306~20.970
	吸烟或被动吸烟	GA	57	2.643	1.389~5.027			13	3.348	0.958~11.699
rs7667857	无吸烟或被动吸烟	AA	11	1.099	0.388~3.109	1 313.024	0.312	7	14.902	1.409~157.64	375.158	0.853
	无吸烟或被动吸烟	GA	30	1.666	0.728~3.814			5	5.443	0.662~44.784
	吸烟或被动吸烟	AA	32	1.748	0,880~3.472			16	8.883	1.839~42.909
	吸烟或被动吸烟	GA	48	1.322	0.745~2.345			15	5.262	1.200~23.068