HTR1A a novel type 1 diabetes susceptibility gene on chromosome 5p13-q13.
HTR1A a novel type 1 diabetes susceptibility gene on chromosome 5p13-q13.
复制标题
Htr1a在5p13-Q13染色体上的一种新型1型糖尿病易感基因。
DOI：
10.1371/journal.pone.0035439
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kockum I
中科院分区：
文献类型：
--
作者：
Asad S;Nikamo P;Gyllenberg A;Bennet H;Hansson O;Wierup N;Diabetes Incidence in Sweden Study Group;Carlsson A;Forsander G;Ivarsson SA;Larsson H;Lernmark Å;Lindblad B;Ludvigsson J;Marcus C;Rønningen KS;Nerup J;Pociot F;Luthman H;Fex M;Kockum I
我们之前在斯堪的纳维亚1型糖尿病（T1D）家族中进行了全基因组连锁研究。在瑞典家庭中，我们检测到染色体5p13-q13区域的提示连锁（LOD≤2.2）。我们研究的目的是研究相关区域，寻找可能的T1D易感基因。在斯堪的纳维亚家族中对微卫星进行基因分型，以精细绘制先前相关区域。此外，对瑞典和丹麦家庭以及瑞典散发病例的snp进行了基因分型。在瑞典家族中，我们检测到与5-羟色胺受体1A （HTR1A）基因的全基因组显著连锁（LOD 3.98, p<9.8×10−6）。标记两个独立基因的标记；瑞典和丹麦家庭中无名指蛋白180 （RNF180）和HTR1A与T1D存在相关性（p<0.002, p<0.001）。这种联系在零星病例中未得到证实。条件分析表明主要与HTR1A相关。定量PCR结果显示，HTR1A和RNF180转录本均存在于人朗格汉斯胰岛中。此外，免疫组织化学分析证实，5-HTR1A蛋白存在于分离的人朗格汉斯胰岛以及人胰腺切片中。我们已经在两个不同的家族材料中发现并证实了HTR1A和RFN180这两个高连锁不平衡（LD）基因与T1D的关联。由于HTR1A和RFN180在人朗格汉斯胰岛中均以mRNA水平表达，而HTR1A以蛋白形式表达，我们认为HTR1A可能通过调节初始自身免疫攻击或胰岛再生、胰岛素释放或两者同时调节来影响T1D易感性。
We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD≤2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes. Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, p<9.8×10−6). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (p<0.002, p<0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas. We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both.
登录
查看更多内容
影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
影响因子：
9.9
作者：
Hedstrom, Anna K.;Baarnhielm, Maria;Alfredsson, Lars
通讯作者：
Alfredsson, Lars
影响因子：
27.4
作者：
Kling, A.;Seddighzadeh, M.;Padyukov, L.
通讯作者：
Padyukov, L.
影响因子：
30.8
作者：
Lundmark, Frida;Duvefelt, Kristina;Hillert, Jan
通讯作者：
Hillert, Jan
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D