S region gene epitope and gene mutation of HBsAg and HBsAb coexistence patients with genotype B and C

doi:10.3969/j.issn.1673-8640.2016.08.015

Abstract

Abstract:

Objective To investigate the difference between S region gene epitope and gene mutation of hepatitis B surface antigen （HBsAg） and hepatitis B surface antibody （HBsAb） coexistence patients with genotype B and C,and to study the correlation of HBsAg and HBsAb coexistence. Methods A total of 5 HBsAg and HBsAb coexistence patients were enrolled,and 51 S region clones were collected. S regions were amplified and sequenced. Result There were 3 patients with genotype C and 2 patients with genotype B. The amino acid mutation rate in S region of 30 clones with genotype C was higher than that of 21 clones with genotype B,and differences were found in S region N-terminal,C-terminal and major hydrophilic region（MHR）. The mutation loci of clones with genotype C were mainly concentrated in locus 194,68 and 3,while the mutation loci of clones with genotype B were mainly concentrated in locus 40,200,129 and 5. Conclusions There is difference in amino acid mutation in S region among HBsAg and HBsAb coexistence patients（mutation loci and frequencies） between different genotypes,so epitopes with different genotypes are different. Amino acid mutations within epitope region could lead to the antigenicity changes of HBsAg and potential subsequent failure of neutralization by HBsAb,leading to the coexistence of HBsAg and HBsAb.

Key words: Hepatitis B surface antigen, Hepatitis B surface antibody, Coexistence, Genotype, Gene mutation

CLC Number:

R446.62

WANG Shan, CHEN Weiqin, WANG Lei, WANG Qihua, DONG Jingyi, WU Chunyan. S region gene epitope and gene mutation of HBsAg and HBsAb coexistence patients with genotype B and C[J]. Laboratory Medicine, 2016, 31(8): 697-702.

Figures/Tables 4

References 18

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基因分型	S区各区段
基因分型	S区全长（aa1~ 226）	N端（aa1~ 99）	MHR（aa100~ 169）	MHR1（aa100~ 119）	MHR2（aa120~ 123）	MHR3（aa124~ 137）	MHR4（aa138~ 147）	MHR5（aa148~ 169）	C端（aa170~ 226）
C基因型	3.23	3.57	2.14	2.50	-	5.23	2.00	0.30	3.98
B基因型	1.50	1.59	1.22	-	-	3.40	-	1.73	1.67
χ²值	48.99	17.94	17.90	10.66	-	1.363	4.25	6.28	12.75
P值	0.031	<0.001	<0.001	0.001	-	0.243	0.039	0.012	<0.001

基因分型	S区各区段
基因分型	S区全长（aa1~ 226）	N端（aa1~ 99）	MHR（aa100~ 169）	MHR1（aa100~ 119）	MHR2（aa120~ 123）	MHR3（aa124~ 137）	MHR4（aa138~ 147）	MHR5（aa148~ 169）	C端（aa170~ 226）
C基因型	3.23	3.57	2.14	2.50	-	5.23	2.00	0.30	3.98
B基因型	1.50	1.59	1.22	-	-	3.40	-	1.73	1.67
χ²值	48.99	17.94	17.90	10.66	-	1.363	4.25	6.28	12.75
P值	0.031	<0.001	<0.001	0.001	-	0.243	0.039	0.012	<0.001

S区各区段	C基因型		B基因型
S区各区段	变异位点	变异数（变异频次/克隆总数）	变异位点	变异数（变异频次/克隆总数
N端（aa1~99）	T68I S3N C69stop P62L E2G、F8S、G10K、V14G、F19S、R24K、 D33G、N40S、L42P、G44E、P46L、T47K、 W74T/L/stop、L77Q/R、V96A、L98R	29/30 19/30 12/30 9/30 <5/30	N40S A5S L49H G18N/V、W36stop、 S55F、P67L、I82T	11/21 8/21 7/21 <5/21
MHR （aa100~169）	I126S Y100F、Q101K、M103T、V106F、C107Y/R、 L110P、S114A、G119R、T125A/M、 G130K、T131N、M133T、P135S、K141E、 G145R、E164G、W165stop	10/30 <5/30	Q129R Y161F、W163R、 A166G	10/21 <5/21
C端（aa170~226）	A194V W182stop L213I S204R T189I、W191R、P217Q、I218T、F220L/C、 C221Y、W223stop、V224I	30/30 11/30 7/30 6/30 <5/30	F200Y、 M197T、S204N、 N207D、V224A	11/21 <5/21

S区各区段	C基因型		B基因型
S区各区段	变异位点	变异数（变异频次/克隆总数）	变异位点	变异数（变异频次/克隆总数
N端（aa1~99）	T68I S3N C69stop P62L E2G、F8S、G10K、V14G、F19S、R24K、 D33G、N40S、L42P、G44E、P46L、T47K、 W74T/L/stop、L77Q/R、V96A、L98R	29/30 19/30 12/30 9/30 <5/30	N40S A5S L49H G18N/V、W36stop、 S55F、P67L、I82T	11/21 8/21 7/21 <5/21
MHR （aa100~169）	I126S Y100F、Q101K、M103T、V106F、C107Y/R、 L110P、S114A、G119R、T125A/M、 G130K、T131N、M133T、P135S、K141E、 G145R、E164G、W165stop	10/30 <5/30	Q129R Y161F、W163R、 A166G	10/21 <5/21
C端（aa170~226）	A194V W182stop L213I S204R T189I、W191R、P217Q、I218T、F220L/C、 C221Y、W223stop、V224I	30/30 11/30 7/30 6/30 <5/30	F200Y、 M197T、S204N、 N207D、V224A	11/21 <5/21