中华小儿外科杂志
中華小兒外科雜誌
중화소인외과잡지
CHINESE JOURNAL OF PEDIATRIC SURGERY
2013年
1期
10-13
,共4页
蔡春泉%石鸥燕%管卫%沈永明%张庆江%马骁
蔡春泉%石鷗燕%管衛%瀋永明%張慶江%馬驍
채춘천%석구연%관위%침영명%장경강%마효
神经管缺陷%VANGL1基因%多态性,单核苷酸
神經管缺陷%VANGL1基因%多態性,單覈苷痠
신경관결함%VANGL1기인%다태성,단핵감산
Neural tube defects%VANGL1 gene%Polymorphisms,single nucleotide
目的 研究中国北方汉族人群VANGL1基因编码区单核苷酸多态性(SNPs)与神经管发育缺陷(neural tube defects,NTDs)发生的相关性.方法 采用PCR扩增和测序的方法对135例NTDs患儿和135例正常对照者VANGL1基因两个错义单核苷酸多态性(rs4839469 c.346G＞A p.Ala116Thr; rs34059106 c.1040A＞C p.Glu347Ala)进行分析,计算基因型和等位基因分布频率并进行蛋白质空间结构预测.结果 测序结果发现VANGL1基因rs4839469位点同时存在Ala116Thr和Ala116Pro多态性,且该位点在病例-对照组间等位基因与基因型分布均具有统计学差异(P=0.036、0.010),新发现的GC基因型其OR值为9.750；蛋白质空间结构预测结果显示Ala116Pro变异后其所处的a螺旋结构片段明显缩短.而rs34059106位点,在病例组与对照组均表现为等位基因A,未发现等位基因C.结论 中国北方汉族人群中VANGL1基因rs4839469位点多态性与NTDs发生具有明显相关性,基因型GC使NTDs发生的危险度增加,且可能改变蛋白质空间结构从而影响生物学功能的发挥；而rs34059106位点多态性与NTDs发生无明显相关性.
目的 研究中國北方漢族人群VANGL1基因編碼區單覈苷痠多態性(SNPs)與神經管髮育缺陷(neural tube defects,NTDs)髮生的相關性.方法 採用PCR擴增和測序的方法對135例NTDs患兒和135例正常對照者VANGL1基因兩箇錯義單覈苷痠多態性(rs4839469 c.346G＞A p.Ala116Thr; rs34059106 c.1040A＞C p.Glu347Ala)進行分析,計算基因型和等位基因分佈頻率併進行蛋白質空間結構預測.結果 測序結果髮現VANGL1基因rs4839469位點同時存在Ala116Thr和Ala116Pro多態性,且該位點在病例-對照組間等位基因與基因型分佈均具有統計學差異(P=0.036、0.010),新髮現的GC基因型其OR值為9.750；蛋白質空間結構預測結果顯示Ala116Pro變異後其所處的a螺鏇結構片段明顯縮短.而rs34059106位點,在病例組與對照組均錶現為等位基因A,未髮現等位基因C.結論 中國北方漢族人群中VANGL1基因rs4839469位點多態性與NTDs髮生具有明顯相關性,基因型GC使NTDs髮生的危險度增加,且可能改變蛋白質空間結構從而影響生物學功能的髮揮；而rs34059106位點多態性與NTDs髮生無明顯相關性.
목적 연구중국북방한족인군VANGL1기인편마구단핵감산다태성(SNPs)여신경관발육결함(neural tube defects,NTDs)발생적상관성.방법 채용PCR확증화측서적방법대135례NTDs환인화135례정상대조자VANGL1기인량개착의단핵감산다태성(rs4839469 c.346G＞A p.Ala116Thr; rs34059106 c.1040A＞C p.Glu347Ala)진행분석,계산기인형화등위기인분포빈솔병진행단백질공간결구예측.결과 측서결과발현VANGL1기인rs4839469위점동시존재Ala116Thr화Ala116Pro다태성,차해위점재병례-대조조간등위기인여기인형분포균구유통계학차이(P=0.036、0.010),신발현적GC기인형기OR치위9.750；단백질공간결구예측결과현시Ala116Pro변이후기소처적a라선결구편단명현축단.이rs34059106위점,재병례조여대조조균표현위등위기인A,미발현등위기인C.결론 중국북방한족인군중VANGL1기인rs4839469위점다태성여NTDs발생구유명현상관성,기인형GC사NTDs발생적위험도증가,차가능개변단백질공간결구종이영향생물학공능적발휘；이rs34059106위점다태성여NTDs발생무명현상관성.
Objective To study the association of single nucleotide polymorphisms (SNPs) of the VANGL1 gene and neural tube defects (NTDs) in the Han population of northern China.Methods The SNPs were genotyped and sequenced by polymerase chain reaction (PCR) in 135 NTD patients and paired normal controls.The genotypes and allele frequencies were calculated and analyzed to examine the correlation between VANGL1 SNPs and NTDs.Prediction of 3-D protein structure was conducted by CPHmodels platform.Results We found two nonsynonymous SNPs in the VANGL1 gene which lead to amino acid changes (rs4839469 c.346G＞A p.Ala116Thr; rs34059106 c.1040A＞C p.Glu347Ala).Both G＞A (Ala116Thr) and G＞C (Ala116Pro) polymorphisms at codon 116 of VANGL1 gene were identified.Significant associations were found between the VANGL1 codon 116 polymorphism and NTDs (P =0.036 and 0.010 for allele and genotype frequencies,respectively).The odd ratio of the GC genotype was 9.750.The 3-D protein structure prediction showed that the VANGL1 gene codon 116 Pro mutant had shortened a-helix than that of wild type.The Glu347Ala variant was not detected in both groups.Conclusions The rs4839469,not the rs34059106 of VANGL1 is associated with NTDs in Han population of northern China.The GC genotype may increase risk for NTDs.
