Investigation of the vitamin D receptor gene (VDR) and its interaction with protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2) on risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY).
Investigation of the vitamin D receptor gene (VDR) and its interaction with protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2) on risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY).
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DOI：
10.1016/j.jsbmb.2012.08.012
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发表时间：
2013-01
影响因子：
4.1
通讯作者：
Norris, J. M.
中科院分区：
文献类型：
--
作者：
Frederiksen, B.;Liu, E.;Romanos, J.;Steck, A. K.;Yin, X.;Kroehl, M.;Fingerlin, T. E.;Erlich, H.;Eisenbarth, G. S.;Rewers, M.;Norris, J. M.
本研究调查了维生素D受体基因（VDR）和蛋白酪氨酸磷酸酶，非受体2型基因（PTPN 2）的变体之间的关联，以及VDR和PTPN 2之间的相互作用和胰岛自身免疫（IA）和进展为1型糖尿病（T1 D）的风险。自1993年以来，年轻人糖尿病自身免疫研究（DAISY）一直在跟踪T1 D风险增加的儿童。在1692例基因分型为VDR rs 1544410、VDR rs 2228570、VDR rs 11568820、PTPN 2 rs 1893217和PTPN 2 rs 478582的DAISY儿童中，111例发生IA，定义为连续2次或多次访视时GAD、胰岛素或IA-2自身抗体阳性，38例IA阳性儿童进展为T1 D。进行了比例风险回归分析。IA发生与任何基因变异之间均无关联，也无VDR* PTPN 2相互作用的证据。IA阳性儿童进展为T1 D与VDR rs 2228570 GG基因型相关（HR：0.49，95% CI：0.26-0.92），VDR rs 1544410和PTPN 2 rs 1893217之间存在相互作用（pinteraction = 0.02）。在PTPN 2 rs 1893217 AA基因型儿童中，VDR rs 1544410 AA/AG基因型与T1 D风险降低相关（HR：0.24，95% CI：0.11-0.53，p = 0.0004），而在PTPN 2 rs 1893217 GG/GA基因型儿童中，VDR rs 1544410 AA/AG基因型与T1 D无关（人力资源：1.32，95% CI：0.43-4.06，p = 0.62）。这些发现应在更大的队列中重复进行确认。VDR和PTPN 2多态性在T1 D进展风险中的相互作用提供了关于维生素D在T1 D病因学中作用的见解。
The present study investigated the association between variants in the vitamin D receptor gene (VDR) and protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2), as well as an interaction between VDR and PTPN2 and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D). The Diabetes Autoimmunity Study in the Young (DAISY) has followed children at increased risk of T1D since 1993. Of the 1692 DAISY children genotyped for VDR rs1544410, VDR rs2228570, VDR rs11568820, PTPN2 rs1893217, and PTPN2 rs478582, 111 developed IA, defined as positivity for GAD, insulin or IA-2 autoantibodies on 2 or more consecutive visits, and 38 IA positive children progressed to T1D. Proportional hazards regression analyses were conducted. There was no association between IA development and any of the gene variants, nor was there evidence of a VDR*PTPN2 interaction. Progression to T1D in IA positive children was associated with the VDR rs2228570 GG genotype (HR: 0.49, 95% CI: 0.26–0.92) and there was an interaction between VDR rs1544410 and PTPN2 rs1893217 (pinteraction = 0.02). In children with the PTPN2 rs1893217 AA genotype, the VDR rs1544410 AA/AG genotype was associated with a decreased risk of T1D (HR: 0.24, 95% CI: 0.11–0.53, p = 0.0004), while in children with the PTPN2 rs1893217 GG/GA genotype, the VDR rs1544410 AA/AG genotype was not associated with T1D (HR: 1.32, 95% CI: 0.43–4.06, p = 0.62). These findings should be replicated in larger cohorts for confirmation. The interaction between VDR and PTPN2 polymorphisms in the risk of progression to T1D offers insight concerning the role of vitamin D in the etiology of T1D.
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影响因子：
6.2
作者：
Fang, Y;Van Meurs, JBJ;Uitterlinden, AG
通讯作者：
Uitterlinden, AG
影响因子：
13.6
作者：
Angel, B;Santos, JL;Pérez-Bravo, F
通讯作者：
Pérez-Bravo, F
影响因子：
2.7
作者：
Lemos, Manuel C.;Fagulha, Ana;Carvatheiro, Manuela
通讯作者：
Carvatheiro, Manuela
影响因子：
6.4
作者：
Lurie, Galina;Wilkens, Lynne R.;Thompson, Pamela J.;Carney, Michael E.;Palmieri, Rachel T.;Pharoah, Paul D. P.;Song, Honglin;Hogdalls, Estrid;Kjaer, Susanne Kruger;DiCioccio, Richard A.;McGuire, Valerie;Whittemore, Alice S.;Gayther, Simon A.;Gentry-Maharaj, Aleksandra;Menon, Usha;Ramus, Susan J.;Goodman, Marc T.
通讯作者：
Goodman, Marc T.
影响因子：
8.2
作者：
McDermott, MF;Ramachandran, A;Hitman, GA
通讯作者：
Hitman, GA