Associations of genetic variants in endocytic trafficking of epidermal growth factor receptor super pathway with risk of nonsyndromic cleft lip with or without cleft palate

被引：10

作者：

Li, Bing ^{[1
,2
]}

Ma, Lan ^{[3
]}

Zhang, Chi ^{[4
]}

Zhou, Zhixuan ^{[5
]}

Yuan, Hua ^{[2
,3
]}

Jiang, Hongbing ^{[2
,3
]}

Pan, Yongchu ^{[3
,4
,6
]}

Tan, Qian ^{[1
,7
]}

机构：

[1] Nanjing Med Univ, Drum Tower Clin Med Coll, Dept Burns & Plast Surg, Nanjing, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Affiliated Hosp Stomatol, Dept Oral & Maxillofacial Surg, Nanjing, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Jiangsu Key Lab Oral Dis, Nanjing, Jiangsu, Peoples R China

[4] Nanjing Med Univ, Dept Orthodont, Affiliated Hosp Stomatol, Nanjing, Jiangsu, Peoples R China

[5] Nanjing Med Univ, Affiliated Hosp Stomatol, Dept Polyclin, Nanjing, Jiangsu, Peoples R China

[6] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China

[7] Nanjing Univ, Med Sch, Affiliated Drum Tower Hosp, Dept Burns & Plast Surg, Nanjing, Jiangsu, Peoples R China

来源：

MOLECULAR GENETICS & GENOMIC MEDICINE | 2018年 / 6卷 / 06期

基金：

中国国家自然科学基金;

关键词：

endocytosis; epidermal growth factor receptor; genome-wide association study; nonsyndromic cleft lip with or without cleft palate; pathway; single-nucleotide polymorphism; GENOME-WIDE ASSOCIATION; POPULATION-BASED COHORT; FOCAL ADHESION KINASE; NEURAL CREST; METAANALYSES; MECHANISMS; MESENCHYME; FOREBRAIN; IDENTIFY; ELEMENTS;

D O I：

10.1002/mgg3.497

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background The genetic etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) has not been fully clarified to date. Epidermal growth factor receptor (EGFR) was reportedly involved in its biological establishment and regulation of cell migration during the embryonic stage. Methods We selected a super pathway of endocytic trafficking of EGFR and investigated the associations of single-nucleotide polymorphisms (SNPs) in the super pathway with the risk of NSCL/P by analyzing our published genome-wide association study (GWAS) data from 504 NSCL/P individuals and 455 controls. After the false discovery rate (FDR) control, we conducted linkage disequilibrium (LD) analyses and conditional regression analyses to obtain independent lead SNPs. We performed LD analyses between the lead SNPs and the reported SNPs to find novel ones from our study. We annotated the lead SNPs and investigated their mapped genes in silico. Results A total of 82 SNPs showed a statistical association with the risk of NSCL/P after FDR control. They contained three reported SNPs which were g.117068049G>A (rs7078160), g.117086783C>G (rs10886040), and g.117101266G>T (rs17095681). Four independent lead SNPs were obtained, including g.116979803 T>C (rs1905539) and g.117037960A>G (rs7902502) at 10q25.3, g.35720163G>C (rs75656820) at 17q12, and g.156864512G>A (rs1800877) at 1q23.1. Three of them were in low LD (r(2) < 0.5) with the reported SNPs except g.117037960A>G (rs7902502), so these three were newly identified. Lead SNPs were mapped to three genes: SHTN1, AP2B1, and NTRK1. The three genes were relatively more highly expressed in the human craniofacial region and in the proximal maxillary location during the craniofacial development stage of the embryonic mouse. Conclusion Our results suggested that SHTN1, AP2B1, and NTRK1 might be associated with the development of NSCL/P.

引用

页码：1157 / 1167

页数：11

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