1型糖尿病胰岛自身抗体与HLA-DQ基因型的关系
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摘要
第一部分 中国汉族正常人群胰岛自身抗体与HLA-DQ基因型频率分布
目的：探讨中国汉族正常人群谷氨酸脱羧酶抗体(GADA)、蛋白酪氨酸磷酸酶抗体(IA-2A)及胰岛素自身抗体(IAA)的检出率及HLA-DQ基因型频率分布。
方法：采用放射配体法检测376例中国汉族正常人群GADA、IA-2A与300例正常人群IAA，其中278例采用PCR-直接测序法确定HLA-DQ基因型。
结果：①376例正常人群GADA、IA-2A与IAA阳性率分别为1.06％、0.53％与1.00％，与美国LaGasse等、日本、韩国、中国香港、台湾地区报道的结果差异无显著性(P＞0.05)，GADA检出率仅低于德国Strebelow等报道的2.97％(P＜0.05)，IA-2A检出率仅低于Bingley等报道的2.52％(P＜0.05)。②我国正常人群高危基因型DQB1*0201／0302、中危基因型DQB1*0302／X(X为*0302或非*0301、*0602的其他基因)与保护性基因型DQB1*0602／X(X为*0602或非0302的其他基因)频率均低于高加索人(分别为0.8％vs2.7％～3.3％、5.2％vs8.8％～10.8％与37.9％vs46.7％～64.2％)(P＜0.05)，低危基因型频率(19.0％vs19.8％～24.9％)差异无显著性。高加索人高危、中危、保护性基因型频率分别是我国的3～4倍、2倍与1.5倍。③我国正常人群单体型以DQA1*03-DQB1*0303频率最高(15.3％)，高危单体型DQA1*03-DQB1*0302与保护单体型DQA1*0102-DQB1*0602频率低于高加索人(3.8％vs7.4％～19.3％、5.3％vs12.0％～19.2％，P＜0.05～0.01)，而与日本、韩国及中国台湾人群比较无统计学差异(P＞0.05)。④5例已进行HLA-DQ基因分型的抗体阳性者80％携带1个易感单体型。
结论：①中国汉族正常人群HLA-DQB1高危与中危基因型频率低于高加索人，可能是我国T1DM发病率低的主要原因。②携带易感单体型的正常人群自身抗体阳性率增加，需随访观察。
Part 1 Relationship between Islet Autoantibodies and HLA-DQ Genotypes in Healthy Controls
Objective: To investigate the frequencies of GADA, IA-2A, IAA and HLA-DQ genotypes in Chinese Han population.
Methods: 376 healthy Han controls were recruited and measured for GADA and IA-2A, 300 ones were measured for IAA. Among them, 278 ones were typed for the polymorphisms of HLA-DQ genotypes with PCR sequencing-based typing method.
Results: ①The positivity frequencies of GADA, IA-2A and IAA in 376 controls were 1.06%, 0.53% and 1.00%, respectively, which were nearly close to those of American ( reported by LaGasse),Japan, Korea,Taiwan and Hongkong, but GADA positivity was lower than that of Germany (2.97%,reported by Strebelow) and IA-2A positivity was lower than that of England (2.52%,reported by Bingley) (P<0.05).②The frequencies of high risk DQB1~*0201/0302 genotype,moderate risk DQBl~*0302/X(X indicates~*0302 or a nondefined allele) ones and DQBl~*0602/X(X indicates ~*0602 or a nondefined allele) decreased ones in Chinese Han controls were all lower than those of Caucasian (0.8%vs2.7%~3.3%, 5.2%vs 8.8% -10.8% and 37.9%vs46.7%~64.2%, respectively, P<0.05 ), and the difference was not significant for low risk genotypes (19.0% vs 19.8%~ 24.9%) . The frequencies of high, moderate and decreased risk genotypes in Caucasian were 3-4, 2 and 1.5 times higher than those in Chinese controls. ③The frequency of HLA-DQA1 ~*03-DQB1~*0303 haplotype was highest in Chinese controls, but the frequencies of highest risk DQAl*0301-DQBl*0302 haplotype and decreased risk DQAl~*0102-DQB1~*0602 haplotype were lower than those of Caucasian (3.8%vs7.4%~19.3% and 5.3%vs 12.0% -19.2%, respectively,P<0.05 ) .However, the difference was not significant in Japanese, Korean, Taiwanese and Hongkong. ④Among five healthy controls with autoantibody positivity, four carry one kind of susceptible haplotype.
目的：探讨中国汉族正常人群谷氨酸脱羧酶抗体(GADA)、蛋白酪氨酸磷酸酶抗体(IA-2A)及胰岛素自身抗体(IAA)的检出率及HLA-DQ基因型频率分布。
方法：采用放射配体法检测376例中国汉族正常人群GADA、IA-2A与300例正常人群IAA，其中278例采用PCR-直接测序法确定HLA-DQ基因型。
结果：①376例正常人群GADA、IA-2A与IAA阳性率分别为1.06％、0.53％与1.00％，与美国LaGasse等、日本、韩国、中国香港、台湾地区报道的结果差异无显著性(P＞0.05)，GADA检出率仅低于德国Strebelow等报道的2.97％(P＜0.05)，IA-2A检出率仅低于Bingley等报道的2.52％(P＜0.05)。②我国正常人群高危基因型DQB1*0201／0302、中危基因型DQB1*0302／X(X为*0302或非*0301、*0602的其他基因)与保护性基因型DQB1*0602／X(X为*0602或非0302的其他基因)频率均低于高加索人(分别为0.8％vs2.7％～3.3％、5.2％vs8.8％～10.8％与37.9％vs46.7％～64.2％)(P＜0.05)，低危基因型频率(19.0％vs19.8％～24.9％)差异无显著性。高加索人高危、中危、保护性基因型频率分别是我国的3～4倍、2倍与1.5倍。③我国正常人群单体型以DQA1*03-DQB1*0303频率最高(15.3％)，高危单体型DQA1*03-DQB1*0302与保护单体型DQA1*0102-DQB1*0602频率低于高加索人(3.8％vs7.4％～19.3％、5.3％vs12.0％～19.2％，P＜0.05～0.01)，而与日本、韩国及中国台湾人群比较无统计学差异(P＞0.05)。④5例已进行HLA-DQ基因分型的抗体阳性者80％携带1个易感单体型。
结论：①中国汉族正常人群HLA-DQB1高危与中危基因型频率低于高加索人，可能是我国T1DM发病率低的主要原因。②携带易感单体型的正常人群自身抗体阳性率增加，需随访观察。
Part 1 Relationship between Islet Autoantibodies and HLA-DQ Genotypes in Healthy Controls
Objective: To investigate the frequencies of GADA, IA-2A, IAA and HLA-DQ genotypes in Chinese Han population.
Methods: 376 healthy Han controls were recruited and measured for GADA and IA-2A, 300 ones were measured for IAA. Among them, 278 ones were typed for the polymorphisms of HLA-DQ genotypes with PCR sequencing-based typing method.
Results: ①The positivity frequencies of GADA, IA-2A and IAA in 376 controls were 1.06%, 0.53% and 1.00%, respectively, which were nearly close to those of American ( reported by LaGasse),Japan, Korea,Taiwan and Hongkong, but GADA positivity was lower than that of Germany (2.97%,reported by Strebelow) and IA-2A positivity was lower than that of England (2.52%,reported by Bingley) (P<0.05).②The frequencies of high risk DQB1~*0201/0302 genotype,moderate risk DQBl~*0302/X(X indicates~*0302 or a nondefined allele) ones and DQBl~*0602/X(X indicates ~*0602 or a nondefined allele) decreased ones in Chinese Han controls were all lower than those of Caucasian (0.8%vs2.7%~3.3%, 5.2%vs 8.8% -10.8% and 37.9%vs46.7%~64.2%, respectively, P<0.05 ), and the difference was not significant for low risk genotypes (19.0% vs 19.8%~ 24.9%) . The frequencies of high, moderate and decreased risk genotypes in Caucasian were 3-4, 2 and 1.5 times higher than those in Chinese controls. ③The frequency of HLA-DQA1 ~*03-DQB1~*0303 haplotype was highest in Chinese controls, but the frequencies of highest risk DQAl*0301-DQBl*0302 haplotype and decreased risk DQAl~*0102-DQB1~*0602 haplotype were lower than those of Caucasian (3.8%vs7.4%~19.3% and 5.3%vs 12.0% -19.2%, respectively,P<0.05 ) .However, the difference was not significant in Japanese, Korean, Taiwanese and Hongkong. ④Among five healthy controls with autoantibody positivity, four carry one kind of susceptible haplotype.
引文
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