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HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q13
Karolinska Institute, Sweden .
Karolinska Institute, Sweden .
Karolinska Institute, Sweden .
Lund University, Sweden Lund University, Sweden .
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2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 5Article in journal (Refereed) Published
Abstract [en]

Background: 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 less than= 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. Methodology/Principal Findings: 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, pless than9.8x10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (pless than0.002, pless than0.001 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. Conclusions: 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.

Place, publisher, year, edition, pages
Public Library of Science , 2012. Vol. 7, no 5
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-79826DOI: 10.1371/journal.pone.0035439ISI: 000305340700010OAI: diva2:544401
Available from: 2012-08-14 Created: 2012-08-14 Last updated: 2012-10-19

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Ludvigsson, Johnny
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PediatricsFaculty of Health SciencesDepartment of Paediatrics in Linköping
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