HLA DPA1, DPB1 alleles and haplotypes contribute to the risk associated with type 1 diabetes: analysis of the type 1 diabetes genetics consortium families.
HLA DPA1, DPB1 alleles and haplotypes contribute to the risk associated with type 1 diabetes: analysis of the type 1 diabetes genetics consortium families.
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DOI：
10.2337/db09-0680
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发表时间：
2010-08
期刊：
影响因子：
7.7
通讯作者：
Type 1 Diabetes Genetics Consortium
中科院分区：
文献类型：
--
作者：
Varney MD;Valdes AM;Carlson JA;Noble JA;Tait BD;Bonella P;Lavant E;Fear AL;Louey A;Moonsamy P;Mychaleckyj JC;Erlich H;Type 1 Diabetes Genetics Consortium
目的探讨DPA 1和DPB 1等位基因和单倍型与1型糖尿病的相关性。将1型糖尿病患者中DPA 1和DPB 1等位基因和单倍型的频率与1,771个家系中基于家系的对照频率直接进行比较，并以HLA（B）-DRB 1-DQA 1-DQB 1连锁不平衡为条件。在存在或不存在主要HLA DR-DQ关联的情况下进行相对倾向性分析（RPA），并检查DP单倍型对个体DR-DQ单倍型风险的贡献。8个DPA 1和38个DPB 1等位基因形成74个DPA 1-DPB 1单倍型，19个DPB 1等位基因与多个DPA 1等位基因相关。在两项分析后，1型糖尿病易感性与DPB 1 *0301（DPA 1 *0103-DPB 1 *0301）显著相关，DPB 1 *0402（DPA 1 *0103-DPB 1 *0402）和DPA 1 *0103-DPB 1 *0101具有保护作用，但与DPA 1 *0201-DPB 1 *0101无关。此外，DPB 1 *0202（DPA 1 *0103-DPB 1 *0202）和DPB 1 *0201（DPA 1 *0103-DPB 1 *0201）与高风险和保护性DR-DQ单倍型存在的易感性显著相关。当仅考虑扩展的HLA-A1-B8-DR 3单倍型时，三种相关性（DPB 1 *0301、*0402和 *0202）仍具有统计学显著性，表明单独的DPB 1可能描述与这种保守单倍型相关的风险。HLA DP等位基因和单倍型多样性对1型糖尿病的风险有显著影响; DPB 1 *0301（DPA 1 *0103-DPB 1 *0301）与易感性相关，DPB 1 *0402（DPA 1 *0103-DPB 1 *0402）和DPA 1 *0103-DPB 1 *0101与保护性相关。DPB 1 *0202（DPA 1 *0103-DPB 1 *0202）的易感性相关性以及单个氨基酸和DPA 1或DR 3-DPB 1 *0101阳性单倍型中连锁不平衡基因的贡献作用的其他证据。
To determine the relative risk associated with DPA1 and DPB1 alleles and haplotypes in type 1 diabetes. The frequency of DPA1 and DPB1 alleles and haplotypes in type 1 diabetic patients was compared to the family based control frequency in 1,771 families directly and conditional on HLA (B)-DRB1-DQA1-DQB1 linkage disequilibrium. A relative predispositional analysis (RPA) was performed in the presence or absence of the primary HLA DR-DQ associations and the contribution of DP haplotype to individual DR-DQ haplotype risks examined. Eight DPA1 and thirty-eight DPB1 alleles forming seventy-four DPA1-DPB1 haplotypes were observed; nineteen DPB1 alleles were associated with multiple DPA1 alleles. Following both analyses, type 1 diabetes susceptibility was significantly associated with DPB1*0301 (DPA1*0103-DPB1*0301) and protection with DPB1*0402 (DPA1*0103-DPB1*0402) and DPA1*0103-DPB1*0101 but not DPA1*0201-DPB1*0101. In addition, DPB1*0202 (DPA1*0103-DPB1*0202) and DPB1*0201 (DPA1*0103-DPB1*0201) were significantly associated with susceptibility in the presence of the high risk and protective DR-DQ haplotypes. Three associations (DPB1*0301, *0402, and *0202) remained statistically significant when only the extended HLA-A1-B8-DR3 haplotype was considered, suggesting that DPB1 alone may delineate the risk associated with this otherwise conserved haplotype. HLA DP allelic and haplotypic diversity contributes significantly to the risk for type 1 diabetes; DPB1*0301 (DPA1*0103-DPB1*0301) is associated with susceptibility and DPB1*0402 (DPA1*0103-DPB1*0402) and DPA1*0103-DPB1*0101 with protection. Additional evidence is presented for the susceptibility association of DPB1*0202 (DPA1*0103-DPB1*0202) and for a contributory role of individual amino acids and DPA1 or a gene in linkage disequilibrium in DR3-DPB1*0101 positive haplotypes.
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人类1型糖尿病易感性基因座图与染色体21q22.3。
影响因子：
7.7
作者：
Concannon P;Onengut-Gumuscu S;Todd JA;Smyth DJ;Pociot F;Bergholdt R;Akolkar B;Erlich HA;Hilner JE;Julier C;Morahan G;Nerup J;Nierras CR;Chen WM;Rich SS;Type 1 Diabetes Genetics Consortium
通讯作者：
Type 1 Diabetes Genetics Consortium
DOI：
10.1046/j.1365-2370.2003.00369.x
发表时间：
2003-04-01
期刊：
EUROPEAN JOURNAL OF IMMUNOGENETICS
影响因子：
--
作者：
Al-Hussein, KA;Rama, NR;Tilanus, MG
通讯作者：
Tilanus, MG
影响因子：
2.7
作者：
CESBRON, A;MOREAU, P;BIGNON, JD
通讯作者：
BIGNON, JD
DOI：
10.1111/j.1463-1326.2008.01001.x
发表时间：
2009-02
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Howson JM;Walker NM;Clayton D;Todd JA;Type 1 Diabetes Genetics Consortium
通讯作者：
Type 1 Diabetes Genetics Consortium
DOI：
10.1084/jem.181.5.1847
发表时间：
1995-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hammer J;Gallazzi F;Bono E;Karr RW;Guenot J;Valsasnini P;Nagy ZA;Sinigaglia F
通讯作者：
Sinigaglia F