Correlation Analysis of HLA-DM Gene Polymorphisms with Polio Vaccine-induced Antibody Response
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摘要:
目的 探讨HLA-DM基因多态性与脊髓灰质炎疫苗诱导抗体应答的相关性。 方法 选取355名2～3月龄广西壮族自治区的健康婴幼儿为研究对象，采用Sanger测序法对DMA的外显子3和DMB的外显子2/3总共10个SNPs进行基因分型，在等位基因、基因型和单倍型水平上分析DMA和DMB基因与脊髓灰质炎疫苗诱导抗体应答的相关性。 结果 脊髓灰质炎疫苗诱导的I型抗体应答中，DMA*01:02、DMB*01:01、DMB*01:01/DMB*01:01和DMA*01:02-DMB*01:01在抗体非阳转组中的频率高于阳转组（P < 0.05）；脊灰II型抗体应答中，DMA*01:02、DMA*01:02/DMA*01:02、DMB*01:01/DMB*01:01和DMA*01:02-DMB*01:01在抗体非阳转组中的频率高于阳转组（ P < 0.05）。 结论 DMA*01:02和DMB*01:01等位基因可能与脊髓灰质炎疫苗诱导的I型和II型抗体应答有关。 Abstract:Objective To investigate the correlation between HLA-DM gene polymorphism and antibody response induced by poliomyelitis vaccine. Methods 355 healthy infants aged 2 to 3 months in Guangxi Zhuang Autonomous Region were selected as the study objects, and 10 SNPs of DMA exon 3 and DMB exon 2/3 were genotyped by Sanger sequencing. The correlation between DMA and DMB genes and poliomyelitis vaccine-induced antibody response was analyzed at allele, genotype and haplotype levels. Results In the type I antibody response induced by polio vaccine, the frequencies of DMA*01:02, DMB*01:01, DMB*01:01/DMB*01:01 and DMA*01:02-DMB*01:01 were higher in the non-seroconversion group than in the seroconversion group（P < 0.05）. In the polio type II antibody response, the frequencies of DMA*01:02, DMA*01:02/DMA*01:02, DMB*01:01/DMB*01:01 and DMA*01:02-DMB*01:01 were higher in the non-seroconversion group than in the seroconversion group（ P < 0.05）. Conclusion Alleles DMA*01:02 and DMB*01:01 may be associated with type I and type II antibody responses induced by poliomyelitis vaccine. -
Key words:
- HLA-DM /
- Gene polymorphism /
- Polio vaccine /
- Antibody response
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表 1 HLA-DMA基因分型SNPs位点信息
Table 1. HLA-DMA genotyping SNPs locus information
外显子区域 外显子3 氨基酸编码位点 condon140 condon155 condon184 SNPs rs1063478 rs6926628 rs17214044 rs41555121 DMA*01:01 GTC GGA CGC CGC DMA*01:02 ATC GGA CGC CGC DMA*01:03 GTC GCA CAC CAC DMA*01:04 ATC GGA TGC TGC 
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表 2 HLA-DMB基因分型SNPs位点信息
Table 2. HLA-DMB genotyping SNPs locus information
外显子区域 外显子2 外显子3 氨基酸编码位点 condon10 condon27 condon31 condon53 condon144 condon179 SNPs rs17583782 rs41560814 rs17617333 rs17617321 rs2071555 rs1042337 DMB*01:01 ACC TCC GAT AGC GCG ATT DMB*01:02 ACC TCC GAT AGC GAG ATT DMB*01:03 ACC TCC GAT AGC GCG ACT DMB*01:04 ACC TCC GAT AGC GTG ACT DMB*01:05 ACC TCC GAT AGC GTG ATT DMB*01:06 ACC TTC GAT AGC GAG ACT DMB*01:07 GCC TCC GTT AAC GCG ATT
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表 3 引物序列及片段大小
Table 3. Primers sequence and fragment size
扩增片段 正向引物 反向引物 目的片段长度（bp） DMA外显子3 5′-TCTCCCAAAGCCTGACCC-3′ 5′-AGAAAGAAGCCTCCTCCC-3′ 479 DMB外显子2 5′-ACATTGACCTGTTCTCCCTT-3′ 5′-CTGCACTTCCTGGTAGCC-3′ 358 DMB外显子3 5′-CGATCCACATCTCATTTTCTCTGC-3′ 5′-CTATGCAGGGCCACCATCTG-3-3′ 353
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表 4 研究对象基本情况
Table 4. Basic information on research subjects
血清型 性别/民族 抗体阳转组 抗体非阳转组 χ2 P 频数 频率 频数 频率 I 男 192 0.549 4 0.800 1.260 0.385 女 158 0.451 1 0.200 II 男 159 0.560 37 0.521 0.345 0.557 女 125 0.440 34 0.479 III 男 194 0.551 2 0.667 0.161 1.000 女 158 0.449 1 0.333 I 汉族 113 0.323 1 0.200 0.341 0.675 壮族 237 0.677 4 0.800 II 汉族 90 0.317 24 0.338 0.116 0.733 壮族 194 0.683 47 0.662 III 汉族 113 0.321 1 0.333 0.002 1.000 壮族 239 0.679 2 0.667
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表 5 DMA和DMB各等位基因在抗体阳转组和非阳转组中的频率分布
Table 5. Comparison of frequencies of alleles of DMA and DMB between two groups
基因 血清型 等位基因 抗体阳转组 抗体非阳转组 χ2 P 频数 频率 频数 频率 DMA Ⅰ DMA*01:01 493 0.704 4 0.400 4.347 0.074 DMA*01:02 177 0.253 6 0.600 6.210 0.022* DMA*01:03 30 0.043 0 0.000 0.447 1.000 Ⅱ DMA*01:01 406 0.715 91 0.641 2.958 0.085 DMA*01:02 135 0.238 48 0.338 5.980 0.014* DMA*01:03 27 0.048 3 0.021 1.958 0.241 Ⅲ DMA*01:01 493 0.700 4 0.667 0.032 1.000 DMA*01:02 181 0.257 2 0.333 0.181 1.000 DMA*01:03 30 0.043 0 0.000 0.267 1.000 DMB Ⅰ DMB*01:01 347 0.496 9 0.900 6.446 0.021* DMB*01:02 129 0.184 1 0.100 0.468 0.699 DMB*01:03 193 0.276 0 0.000 3.786 0.070 DMB*01:05 4 0.006 0 0.000 0.057 1.000 DMB*01:07 27 0.039 0 0.000 0.401 1.000 Ⅱ DMB*01:01 275 0.484 81 0.570 3.382 0.066 DMB*01:02 105 0.185 25 0.176 0.059 0.808 DMB*01:03 160 0.282 33 0.232 1.395 0.238 DMB*01:05 4 0.007 0 0.000 1.006 0.589 DMB*01:07 24 0.042 3 0.021 1.386 0.328 Ⅲ DMB*01:01 352 0.500 4 0.667 0.661 0.686 DMB*01:02 129 0.183 1 0.167 0.011 1.000 DMB*01:03 192 0.273 1 0.167 0.338 0.687 DMB*01:05 4 0.006 0 0.000 0.034 1.000 DMB*01:07 27 0.038 0 0.000 0.239 1.000 *P < 0.05。
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表 6 DMA和DMB各基因型在抗体阳转组和非阳转组中的频率分布
Table 6. Comparison of frequencies of genotypes of DMA and DMB between two groups
基因 血清型 基因型 抗体阳转组 抗体非阳转组 χ2 P 频数 频率 频数 频率 DMA I DMA*01:01/DMA*01:01 174 0.497 0 0.000 4.875 0.061 DMA*01:01/DMA*01:02 123 0.351 4 0.800 4.317 0.057 DMA*01:01/DMA*01:03 22 0.063 0 0.000 0.335 1.000 DMA*01:02/DMA*01:02 23 0.066 1 0.200 1.410 0.297 DMA*01:02/DMA*01:03 8 0.023 0 0.000 0.117 1.000 II DMA*01:01/DMA*01:01 142 0.500 32 0.451 0.552 0.457 DMA*01:01/DMA*01:02 102 0.359 25 0.352 0.012 0.912 DMA*01:01/DMA*01:03 20 0.070 2 0.028 1.744 0.272 DMA*01:02/DMA*01:02 13 0.046 11 0.155 10.736 0.001* DMA*01:02/DMA*01:03 7 0.025 1 0.014 0.288 0.703 III DMA*01:01/DMA*01:01 173 0.491 1 0.333 0.298 1.000 DMA*01:01/DMA*01:02 125 0.355 2 0.667 1.257 0.555 DMA*01:01/DMA*01:03 22 0.063 0 0.000 0.200 1.000 DMA*01:02/DMA*01:02 24 0.068 0 0.000 0.219 1.000 DMA*01:02/DMA*01:03 8 0.023 0 0.000 0.070 1.000 DMB I DMB*01:01/DMB*01:01 92 0.263 4 0.800 7.209 0.020* DMB*01:01/DMB*01:02 57 0.163 1 0.200 0.050 1.000 DMB*01:01/DMB*01:03 93 0.266 0 0.000 1.800 0.332 DMB*01:01/DMB*01:07 11 0.031 0 0.000 0.162 1.000 DMB*01:02/DMB*01:02 14 0.040 0 0.000 0.208 1.000 DMB*01:02/DMB*01:03 35 0.100 0 0.000 0.555 1.000 DMB*01:02/DMB*01:07 7 0.020 0 0.000 0.102 1.000 DMB*01:03/DMB*01:03 28 0.080 0 0.000 0.434 1.000 DMB*01:03/DMB*01:07 9 0.026 0 0.000 0.132 1.000 II DMB*01:01/DMB*01:01 67 0.236 29 0.408 8.570 0.003* DMB*01:01/DMB*01:02 51 0.180 7 0.099 2.725 0.099 DMB*01:01/DMB*01:03 78 0.275 15 0.211 1.180 0.277 DMB*01:01/DMB*01:07 10 0.035 1 0.014 0.844 0.476 DMB*01:02/DMB*01:02 10 0.035 4 0.056 0.669 0.492 DMB*01:02/DMB*01:03 27 0.095 8 0.113 0.198 0.656 DMB*01:02/DMB*01:07 5 0.018 2 0.028 0.328 0.631 DMB*01:03/DMB*01:03 23 0.081 5 0.070 0.087 0.768 DMB*01:03/DMB*01:07 9 0.032 0 0.000 2.309 0.214 III DMB*01:01/DMB*01:01 94 0.267 2 0.667 2.408 0.179 DMB*01:01/DMB*01:02 58 0.165 0 0.000 0.591 1.000 DMB*01:01/DMB*01:03 93 0.264 0 0.000 1.074 0.570 DMB*01:01/DMB*01:07 11 0.031 0 0.000 0.097 1.000 DMB*01:02/DMB*01:02 14 0.040 0 0.000 0.124 1.000 DMB*01:02/DMB*01:03 34 0.097 1 0.333 1.876 0.268 DMB*01:02/DMB*01:07 7 0.020 0 0.000 0.061 1.000 DMB*01:03/DMB*01:03 28 0.080 0 0.000 0.259 1.000 DMB*01:03/DMB*01:07 9 0.026 0 0.000 0.079 1.000 *P < 0.05。
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表 7 DMA-DMB单倍型在抗体阳转组和非阳转组中的频率分布
Table 7. Comparison of frequencies of genotypes of DMA and DMB between two groups
血清型 单倍型 抗体阳转组 抗体非阳转组 χ2 P 频数 频率 频数 频率 I DMA*01:01-DMB*01:01 172 0.245 3 0.300 0.156 0.714 DMA*01:01-DMB*01:02 125 0.178 1 0.100 0.416 1.000 DMA*01:01-DMB*01:03 193 0.275 0 0.000 3.786 0.069 DMA*01:02-DMB*01:01 169 0.241 6 0.600 6.825 0.017* DMA*01:03-DMB*01:07 24 0.034 0 0.000 0.354 0.999 II DMA*01:01-DMB*01:01 141 0.248 34 0.239 0.047 0.827 DMA*01:01-DMB*01:02 102 0.179 24 0.169 0.086 0.768 DMA*01:01-DMB*01:03 160 0.281 33 0.232 1.394 0.237 DMA*01:02-DMB*01:01 128 0.225 47 0.330 6.825 0.008* DMA*01:03-DMB*01:07 21 0.036 3 0.021 0.873 0.444 III DMA*01:01-DMB*01:01 173 0.245 2 0.333 0.245 0.639 DMA*01:01-DMB*01:02 125 0.177 1 0.166 0.004 0.999 DMA*01:01-DMB*01:03 192 0.272 1 0.166 0.338 0.999 DMA*01:02-DMB*01:01 173 0.245 2 0.333 0.245 0.639 DMA*01:03-DMB*01:07 24 0.034 0 0.000 0.211 0.999 *P < 0.05。
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