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Genetics and epigenetics in primary Sjogren's syndrome.

ABSTRACT: Primary Sjögren's syndrome (pSS) is considered to be a multifactorial disease, where underlying genetic predisposition, epigenetic mechanisms and environmental factors contribute to disease development. In the last 5 years, the first genome-wide association studies in pSS have been completed. The strongest signal of association lies within the HLA genes, whereas the non-HLA genes IRF5 and STAT4 show consistent associations in multiple ethnicities but with a smaller effect size. The majority of the genetic risk variants are found at intergenic regions and their functional impact has in most cases not been elucidated. Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNAs play a role in the pathogenesis of pSS by their modulating effects on gene expression and may constitute a dynamic link between the genome and phenotypic manifestations. This article reviews the hitherto published genetic studies and our current understanding of epigenetic mechanisms in pSS.

SUBMITTER: Imgenberg-Kreuz J

PROVIDER: S-EPMC8121440 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Genetics and epigenetics in primary Sjögren's syndrome.

Imgenberg-Kreuz Juliana J Rasmussen Astrid A Sivils Kathy K Nordmark Gunnel G

Rheumatology (Oxford, England) 20210501 5

Primary Sjögren's syndrome (pSS) is considered to be a multifactorial disease, where underlying genetic predisposition, epigenetic mechanisms and environmental factors contribute to disease development. In the last 5 years, the first genome-wide association studies in pSS have been completed. The strongest signal of association lies within the HLA genes, whereas the non-HLA genes IRF5 and STAT4 show consistent associations in multiple ethnicities but with a smaller effect size. The majority of t ...[more]

PMID: 30770922

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Genetics of Sjogren's syndrome.

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IgG Autoantigen Array using sera from primary Sjogren's syndrome patients and non-Sjogren's syndrome controls

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Project description:10 saliva samples from patients with primary Sojgren's syndrome and 10 saliva samples from control subjects Keywords: Biomarker development

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Eligibility for clinical trials in primary Sjogren's syndrome: lessons from the UK Primary Sjogren's Syndrome Registry.

Project description:ObjectiveTo identify numbers of participants in the UK Primary Sjögren's Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment.MethodsWe did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data.ResultsIn relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren's Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren's syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren's Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sjögren's Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren's Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%.ConclusionThe UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters.

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Cardiovascular risk factors in women with primary Sjogren's syndrome: United Kingdom primary Sjogren's syndrome registry results.

Project description:ObjectiveTo determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well-characterized primary Sjögren's syndrome (SS) patients and to compare them to healthy controls.MethodsData on cardiovascular risk factors in primary SS patients and controls were collected prospectively using a standardized pro forma. Cardiovascular risk factors were defined according to established definitions. The prevalence of cardiovascular risk factors in the primary SS group was determined and compared to that in the control group.ResultsPrimary SS patients had a higher prevalence of hypertension (28–50% versus 15.5–25.6%; P < 0.01) and hypertriglyceridemia (21% versus 9.5%; P = 0.002) than age- and sex-matched healthy controls. Furthermore, a significant percentage (56%) of hypertensive patients expected to be on antihypertensive treatment according to best practice was not receiving it.ConclusionPrimary SS patients are more than 2 times more likely to experience hypertension and hypertriglyceridemia than age- and sex-matched healthy controls. Additionally, hypertension is underdiagnosed and suboptimally treated in primary SS.

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