Association study of Toll‐like receptor 9 gene polymorphism in Korean patients with systemic lupus erythematosus

Hur, Jin-Wuk; Shin, Hyoung Doo; Park, B.L.; Kim, L.H.; Kim, S.-Y.; Bae, Sang Cheol

doi:10.1111/j.1399-0039.2005.00374.x

Cited by 82 publications

(45 citation statements)

References 19 publications

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“…One can imagine that genetic variation affecting TLR-9 function could affect the threshold for B cell or dendritic cell activation. We have extended the initial findings from the study by Hur and colleagues (6), who reported no association with SLE in 4 polymorphisms found in a 4,334-bp segment of DNA in the vicinity of TLR-9. Our study examined a much (Figure 1).…”

Section: Discussionsupporting

confidence: 68%

“…In surveying this genomic segment, we found no evidence of association with SLE for the 9 polymorphisms and 8 haplotypes tested. Two of the tested SNPs (rs352140 and rs187084) were genotyped in a Korean population (6) in addition to the present UK population, and both were found to have similar allele frequencies in the 2 populations. Results of the 2 studies can therefore be compared directly at these points and are consistent in showing no evidence of association with SLE.…”

Section: Discussionmentioning

confidence: 87%

“…At the time of completion of our current experiment, another group presented their observation that 4 polymorphisms within a 4,334-bp segment of the TLR-9 gene demonstrated no significant association with susceptibility to SLE in a Korean population (6). We pursued a more comprehensive approach to assessing the role of genetic variation in the vicinity of TLR-9 by genotyping our collection of 362 SLE-affected subject/parent trios from the United Kingdom with single-nucleotide polymorphisms (SNPs) that tag all haplotypes with Ͼ0.05 frequency within a genomic segment, starting 30 kb upstream and ending 30 kb down-stream of the TLR-9 gene.…”

mentioning

confidence: 94%

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Genetic variation in toll‐like receptor 9 and susceptibility to systemic lupus erythematosus

Jager¹,

Richardson²,

Vyse³

et al. 2006

Arthritis & Rheumatism

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Objective. Autoantibodies produced by differentiated B cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE). The Toll-like receptor 9 (TLR-9) gene has recently emerged as an important costimulatory molecule for both B cells and dendritic cells that respond to chromatin immune complexes. Genetic variation affecting the function of TLR-9 may therefore increase or decrease the threshold of B cell or dendritic cell activation. This variability in activation threshold may, in turn, affect an individual's susceptibility to SLE. This study assessed the role of genetic variation within the TLR-9 gene in susceptibility to SLE.Methods. We genotyped 362 SLE-affected subject/ parent trios for 10 single-nucleotide polymorphisms (SNPs) covering a 68,742-bp genomic segment that contains the TLR-9 gene and ϳ60 kb of flanking sequence. We analyzed the data using the transmission disequilibrium test.Results. There was no association of susceptibility to SLE with any of the 9 SNPs that generated usable data or the 8 haplotypes found at a frequency of >0.05 in this population. When analyzing the subset of 143 subjects with lupus nephritis, there was also no evidence of association between disease susceptibility and any SNP or haplotype. Conclusion. These results indicate that there is no evidence that common (frequency higher than 5%) alleles of the TLR-9 gene contribute significantly to the genetic risk involved in susceptibility to SLE or lupus nephritis.Toll-like receptor 9 (TLR-9) has recently been implicated in the activation of autoreactive B cells in murine models of systemic lupus erythematosus (SLE) (1-3). Its recognition of CpG nucleotide sequences appears to enhance the activation of B cells via the B cell receptor (1-3). Subsequent studies in humans have shown that dendritic cells are activated by chromatin immune complexes and that this effect is mediated by a cooperation between TLR-9 and Fc␥ receptors (4,5). These observations suggest that genetic variation affecting the costimulatory function of TLR-9 could lead to differences in B cell response to autoantigens and dendritic cell response to chromatin immune complexes. Such genetic variation may have an effect on susceptibility to SLE.At the time of completion of our current experiment, another group presented their observation that 4 polymorphisms within a 4,334-bp segment of the TLR-9 gene demonstrated no significant association with susceptibility to SLE in a Korean population (6). We pursued a more comprehensive approach to assessing the role of genetic variation in the vicinity of TLR-9 by genotyping our collection of 362 SLE-affected subject/parent trios from the United Kingdom with single-nucleotide polymorphisms (SNPs) that tag all haplotypes with Ͼ0.05 frequency within a genomic segment, starting 30 kb upstream and ending 30 kb downDr. De Jager is the William C.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 94%

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Genetic variation in toll‐like receptor 9 and susceptibility to systemic lupus erythematosus

Jager¹,

Richardson²,

Vyse³

et al. 2006

Arthritis & Rheumatism

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“…Извест-но, что такие полиморфизмы (single nucleotide polymorphisms) гена TLR2, как Arg753Gln, T597C ассоциированы с инфекцией, вызванной Candida albicans, M. tuberculosis, цитомегалови-русом, вирусом герпеса простого 2 типа и други-ми патогенами [9,16,17]. Полиморфизмы гена TLR9 G1174A, G1635A, A2848G ассоциированы с системной красной волчанкой, развитием ин-фекции, вызванной HIV-1 и другими заболе-ваниями [5,7]. Вышеперечисленные полимор-физмы располагаются как в LRR-домене TLRs, распознающем патоген, так и в TIR-домене, Полиморфизм TLR при инфекции 2010, Т.…”

Section: ганковская оа медицинская иммунологияunclassified

Association Studies Between Polymorphic Markers Tlr2 and Tlr9, Pre-Term Delivery and Intrauterine Infections

Gankovskaya¹

2014

Med.Imm.Rus

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ИсследованИе ассоцИацИИ полИморфных маркеров генов TLR2 И TLR9 с преждевременнымИ родамИ И внутрИутробным ИнфИцИрованИемГанковская О.А. ГУ НИИ вакцин и сывороток им. И.И. Мечникова РАМН, Москва ГОУ ВПО РГМУ Росздрава, МоскваРезюме. В последние годы активно изучается роль генетических факторов в формировании пол-ноценных механизмов врожденного иммунитета. TLRs играет большую роль в развитии патологии инфекционного генеза при беременности. Цель данного исследования -изучение ассоциации по-лиморфизмов Arg677Trp, Arg753Gln в гене TLR2 и A2848G в гене TLR9 с преждевременными рода-ми инфекционного генеза и внутриутробным инфицированием в русской популяции на территории г. Москвы. Полиморфные маркеры Arg677Trp, Arg753Gln в гене TLR2 были определены в клиниче-ском материале с помощью ПЦР-ПДРФ (с использованием рестриктазы AciI), полиморфный мар-кер A2848G в гене TLR9 был определен с помощью ПЦР в режиме реального времени в присутствии TaqMan зондов. Показано, что аллель Arg полиморфного маркера Arg753Gln гена TLR2 был ассо-циирован с внутриутробной инфекцией. Другой аллель А полиморфного маркера A2848G гена TLR9 ассоциирован со срочными родами при урогенитальной инфекции. Таким образом, полиморфный маркер A2848G можно расценивать в качестве протективного.Ключевые слова: врожденный иммунитет, Toll-подобные рецепторы, полиморфизм, преждевременные роды, урогениальная инфекция. Gankovskaya O.A. AssociAtion studies between polymorphic mArkers tlr2 And tlr9, pre-term delivery And intrAuterine infectionsАbstract. During last years, a role of genetic factors in maturation of innate immunity functions was actively studied. It is known, that some SNP in TLR9 and TLR2 genes are known to be associated with development of infection in pregnancy. However, interrelations of various TLR-mediated anti-infectious mechanisms with genetic factors in pregnant women were poorly studied. The aim of present study was to evaluate associations between the following SNPs: Arg677Trp, Arg753Gln of TLR2 gene, A2848G SNP of TLR9 gene, and frequencies of pre-term birth complicated by infections in Russian population of Moscow City. SNPs Arg677Trp, Arg753Gln in TLR2 gene have been studied in a clinical material by means of PCR-RFLP analysis, using AciI restrictase. A2848G polymorphic marker in TLR9 gene was assessed by real-time PCR, employing TaqMan probes. It has been shown, that Arg allele of Arg753Gln TLR2 gene was associated with urogenital infections. When studying A2848G polymorphism in TLR9 gene, the A Allele was associated with normal delivery, thus assuming the A2848G polymorphic marker as a protective one. (Med. Immunol., vol. 12, N 1-2, pp 87-94)

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“…One study in Korean patients showed that TLR9 gene polymorphisms were not significantly associated with susceptibility to SLE and related phenotypes [35]. It is likely that other TLRs (TLR7, TLR3?)…”

Section: The External World-infections and Autoantigens (Molecular MImentioning

confidence: 99%

Key autoantigens in SLE

Riemekasten¹,

Hahn²

2005

Rheumatology

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Association study of Toll‐like receptor 9 gene polymorphism in Korean patients with systemic lupus erythematosus

Cited by 82 publications

References 19 publications

Genetic variation in toll‐like receptor 9 and susceptibility to systemic lupus erythematosus

Genetic variation in toll‐like receptor 9 and susceptibility to systemic lupus erythematosus

Association Studies Between Polymorphic Markers Tlr2 and Tlr9, Pre-Term Delivery and Intrauterine Infections

Key autoantigens in SLE

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