Association between genetic variants in the tumour necrosis factor/lymphotoxin alpha/lymphotoxin beta locus and primary Sjogrens syndrome in Scandinavian samples

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Association between genetic variants in the tumour necrosis factor/lymphotoxin alpha/lymphotoxin beta locus and primary Sjogrens syndrome in Scandinavian samples

Isine Bolstad, Anne (author): University of Bergen

Le Hellard, Stephanie (author): University of Bergen

Kristjansdottir, Gudlaug (author): Uppsala University

Vasaitis, Lilian (author): Uppsala University

Kvarnstrom, Marika (author): Karolinska Institute

Sjöwall, Christoffer (author): Östergötlands Läns Landsting,Linköpings universitet,Reumatologi,Hälsouniversitetet,Reumatologiska kliniken i Östergötland

Joar Auglaend Johnsen, Svein (author): Stavanger University Hospital

Eriksson, Per (author): Östergötlands Läns Landsting,Linköpings universitet,Reumatologi,Hälsouniversitetet,Njurmedicinska kliniken US

Omdal, Roald (author): Stavanger University Hospital

Brun, Johan G (author): University of Bergen

Wahren-Herlenius, Marie (author): Karolinska Institute

Theander, Elke (author): Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine

Syvanen, Ann-Christine (author): Uppsala University

Ronnblom, Lars (author): Uppsala University

Nordmark, Gunnel (author): Uppsala University

Jonsson, Roland (author): University of Bergen

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(creator_code:org_t)

2012-01-30
2012
English.
In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 71:6, s. 981-988

Related links:: https://liu.diva-por... (primary) (Raw object); show more...; http://liu.diva-port...; http://dx.doi.org/10...; https://urn.kb.se/re...; https://doi.org/10.1...; https://lup.lub.lu.s...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Objectives Lymphotoxin beta (LTB) has been found to be upregulated in salivary glands of patients with primary Sjogrens syndrome (pSS). An animal model of pSS also showed ablation of the lymphoid organisation and a marked improvement in salivary gland function on blocking the LTB receptor pathway. This study aimed to investigate whether single-nucleotide polymorphisms (SNP) in the lymphotoxin alpha (LTA)/LTB/tumour necrosis factor (TNF) gene clusters are associated with pSS. less thanbrgreater than less thanbrgreater thanMethods 527 pSS patients and 532 controls participated in the study, all of Caucasian origin from Sweden and Norway. 14 SNP markers were genotyped and after quality control filtering, 12 SNP were analysed for their association with pSS using single marker and haplotype tests, and corrected by permutation testing. less thanbrgreater than less thanbrgreater thanResults Nine markers showed significant association with pSS at the p=0.05 level. Markers rs1800629 and rs909253 showed the strongest genotype association (p=1.64E-11 and p=4.42E-08, respectively, after correcting for sex and country of origin). When the analysis was conditioned for the effect of rs1800629, only the association with rs909253 remained nominally significant (p=0.027). In haplotype analyses the strongest effect was observed for the haplotype rs909253G_rs1800629A (p=9.14E-17). The associations were mainly due to anti-Ro/SSA and anti-La/SSB antibody-positive pSS. less thanbrgreater than less thanbrgreater thanConclusions A strong association was found between several SNP in the LTA/LTB/TNF alpha locus and pSS, some of which led to amino acid changes. These data suggest a role for this locus in the development of pSS. Further studies are needed to examine if the genetic effect described here is independent of the known genetic association between HLA and pSS.

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By the author/editor: Isine Bolstad, A ...; Le Hellard, Step ...; Kristjansdottir, ...; Vasaitis, Lilian; Kvarnstrom, Mari ...; Sjöwall, Christo ...; show more...; Joar Auglaend Jo ...; Eriksson, Per; Omdal, Roald; Brun, Johan G; Wahren-Herlenius ...; Theander, Elke; Syvanen, Ann-Chr ...; Ronnblom, Lars; Nordmark, Gunnel; Jonsson, Roland; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

Articles in the publication: Annals of the Rh ...

By the university: Linköping University; Lund University

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Association between genetic variants in the tumour necrosis factor/lymphotoxin alpha/lymphotoxin beta locus and primary Sjogrens syndrome in Scandinavian samples

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