CAJ | 학술논문

目的分析HBV反转录酶区rtM204位点Y(I/V)DD变异及其模式与基因型、亚型的相关性.方法用MEGA4软件对来自基因库/欧洲分子生物学实验室/日本DNA数据库的2849株人类HBV全基因序列进行精准分型,反转录酶区氨基酸对齐排列,统计各位点变异频数.用非参数检验分析变异类别、模式与基因型的关系.结果Y(I/V)DD变异毒株共217株,15种变异模式.其中YIDD变异120株,12种变异模式,其基因型分布为:A型(2株)、B型(B2亚型19株)、C型(C1亚型1株、C2亚型78株和C5亚型1株)、D型(17株)、E型(1株)、G型(1株);YVDD变异97株,9种变异模式,其基因型分布为:A型(17株)、B型(B2亚型22株)、C型(C1亚型3株和C2亚型48株)、D型(3株)、G型(3株)、H型(1株).Y(I/V)DD在基因型A～D型(x2=25.558,P<0.01)、A～C型(X2=17.814,P<0.01)及A与B型(x2=7.198,P<0.01)分布差异均有统计学意义.Y(I/V)DD在基因型B～D型(x2=8.430,P<0.05)及C与D型(X2=8.430,P<0.05)分布差异均有统计学意义.Y(I/V)DD在基因型B与C型(x2=2.756,P=0.10)分布差异无统计学意义.YIDD主要变异模式在基因型A～D型(x2=0.832,P=0.87)及B2与C2亚型(X2=1.928,P=0.75)分布差异均无统计学意义;YVDD主要变异模式在基因型A～D型(X2=16.447,P<0.01)分布差异有统计学意义,其中rtM204V-rtL180M和rtM204V-rtL180M-rtV173L模式在B2～C2亚型(x2=9.531,P<0.01)分布差异有统计学意义.发生YVDD变异时,B2亚型以rtM204V-rtL180M模式为主,rtM204V-rtL180M-rtV173L具有C2亚型高度选择性.结论Y(I/V)DD变异及其模式具有基因型选择性倾向,C2亚型Y(I/V)DD模式比其他基因型更具多样性、独特性和复杂性.
목적 분석HBV반전록매구rtM204위점Y(I/V)DD변이급기모식여기인형、아형적상관성.방법용MEGA4연건대래자기인고/구주분자생물학실험실/일본DNA수거고적2849주인류HBV전기인서렬진행정준분형,반전록매구안기산대제배렬,통계각위점변이빈수.용비삼수검험분석변이유별、모식여기인형적관계.결과Y(I/V)DD변이독주공217주,15충변이모식.기중YIDD변이120주,12충변이모식,기기인형분포위:A형(2주)、B형(B2아형19주)、C형(C1아형1주、C2아형78주화C5아형1주)、D형(17주)、E형(1주)、G형(1주);YVDD변이97주,9충변이모식,기기인형분포위:A형(17주)、B형(B2아형22주)、C형(C1아형3주화C2아형48주)、D형(3주)、G형(3주)、H형(1주).Y(I/V)DD재기인형A～D형(x2=25.558,P<0.01)、A～C형(X2=17.814,P<0.01)급A여B형(x2=7.198,P<0.01)분포차이균유통계학의의.Y(I/V)DD재기인형B～D형(x2=8.430,P<0.05)급C여D형(X2=8.430,P<0.05)분포차이균유통계학의의.Y(I/V)DD재기인형B여C형(x2=2.756,P=0.10)분포차이무통계학의의.YIDD주요변이모식재기인형A～D형(x2=0.832,P=0.87)급B2여C2아형(X2=1.928,P=0.75)분포차이균무통계학의의;YVDD주요변이모식재기인형A～D형(X2=16.447,P<0.01)분포차이유통계학의의,기중rtM204V-rtL180M화rtM204V-rtL180M-rtV173L모식재B2～C2아형(x2=9.531,P<0.01)분포차이유통계학의의.발생YVDD변이시,B2아형이rtM204V-rtL180M모식위주,rtM204V-rtL180M-rtV173L구유C2아형고도선택성.결론Y(I/V)DD변이급기모식구유기인형선택성경향,C2아형Y(I/V)DD모식비기타기인형경구다양성、독특성화복잡성.
Objective To investigate the relationship between the mutation patterns of rtM204V/I (methionine to valine or isoleucine at position rt204 of reverse transcriptase domain)in hepatitis B virus (HBV)polymerase gene and HBV genotypes.Methods A total of 2849 HBV complete genome sequences were retrieved from the GenBank/EMBL/DDBJ.HBV genotypes were determined by using MEGA4 software.The amino acid sequences of the reverse transcriptase(RT)domain were aligned.Data were analyzed using SPSS 13.0.RESULTS Among the 2849 HBV complete genome sequences,217 strains with Y(I/V)DD were identified.Of them,120 had YIDD mutation and the genotype/subgenotype distribution was as follows:A(2),B(B2 19),C(C1 1,C2 78,C5 1),D(17),E(1),G(1);97 had YVDD mutation and the genotype/subgenotype distribution was as follows: A(17),B(B2 22),C(C1 3,C2 48),D(3),G(3),H(1). There is a significant difference in the mutation patterns of Y (I/V) DD among genotypes of A-D,A-C,and between genotype A and B,P < 0.01.There is a difference in the mutation pattern of Y (I/V) DD among genotypes of B-D,between genotype C and D,P < 0.05. Genotype A has a higher tendency to develop YVDD mutation,whereas genotype D has a higher frequency to develop YIDD mutation. The rtM204V-rtL180M mutations were more frequently found in subgenotype B2 than in subgenotype C2 while the rtM204V-rtL 180M-rtV173L mutations were more associated with subgenotype C2 (P < 0.01). Conclusion Different HBV genotype/subgenotype may select different mutation pattern in the YMDD domain. Subgenotype C2 is more diversity and complexity than other HBV genotypes/subgenotypes.