Psoriasis in Norwegian twins: contribution of genetic and environmental effects

Grjibovski, Andrej M.; Olsen, Anne O.; Magnus, Per; Harris, J.R.

doi:10.1111/j.1468-3083.2007.02268.x

Cited by 78 publications

(67 citation statements)

References 29 publications

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“…Considering the negative regulating function of SFRPs, we hypothesized that CpG methylation also occurred in the promoter of SFRPs in psoriasis, which might cause the decreased expression of SFRPs. Interestingly, the discordance rate for psoriasis among monozygotic twins is 35-72%, which also strongly suggests the contribution of epigenetic or environmental factors in the pathogenesis of disease (19)(20)(21). DNA methylation, a critical epigenetic modification of the genome, is involved in the regulation of several developmental and cellular processes, including transcription, embryonic development, X-chromosome inactivation, chromosome stability, and genomic imprinting (22).…”

mentioning

confidence: 99%

Epigenetic Downregulation of SFRP4 Contributes to Epidermal Hyperplasia in Psoriasis

Bai

Liu

et al. 2015

The Journal of Immunology

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Psoriasis is a chronic recurrent inflammatory skin disorder characterized by the dysregulated cross-talk between epidermal keratinocytes and immune cells, leading to keratinocyte hyperproliferation. Several studies demonstrated that Wnt pathway genes were differentially expressed in psoriatic plaques and likely were involved in the pathophysiology of disease. However, the molecular mechanisms underlying Wnt signaling regulation in epidermal hyperplasia in psoriasis remain largely unknown. We report that the expression of secreted frizzled-related protein (SFRP) 4, a negative regulator of the Wnt signaling pathway, was diminished in lesional skin of mouse models and patients with psoriasis. SFRP4 directly inhibited excessive keratinocyte proliferation evoked by proinflammatory cytokines in vitro. Pharmacological inhibition of Wnt signaling or intradermal injection of SFRP4 decreased the severity of the psoriasiform skin phenotype in vivo, including decreased acanthosis and reduced leukocyte infiltration. Mechanistically, we identified that aberrant promoter methylation resulted in epigenetic downregulation of SFRP4 in inflamed skin of patients with psoriasis and in the IL-23–induced mouse model. Our findings suggest that this epigenetic event is critically involved in the pathogenesis of psoriasis, and the downregulation of SFRP4 by CpG island methylation is one possible mechanism contributing to the hyperplasia of epidermis in the disease.

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mentioning

confidence: 99%

Epigenetic Downregulation of SFRP4 Contributes to Epidermal Hyperplasia in Psoriasis

Bai

Liu

et al. 2015

The Journal of Immunology

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“…In epidemiology, it is of interest to determine what proportion of the phenotypic variance each of these factors can explain. Greater phenotype concordance in MZ twins would point to a higher contribution of genetics to the disease (35)(36)(37)(38). The heritable and environmental factors contributing to certain diseases can be seen on table 2.…”

Section: The Discordant Mz Twin Model and Epigeneticsmentioning

confidence: 99%

Epigenetic Basis of Twin Discordance in Diseases: Future Benefits

Demir

2018

Gynecol Obstet Reprod Med

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Monozygotic twins share the same genotype since they are derived from the same zygote. However, monozygotic twin siblings frequently present many phenotypic differences, such as their susceptibilities to diseases. These isogenic individuals are not entirely identical. They exhibit phenotypic incompatibility for many features, from birth weight to complex diseases. Recently, several studies have been published showing that phenotypic differences, especially in monozygotic twins, are being induced from prenatal period to life-long epigenetic differences. Epigenetic studies on twins have a great potential to contribute to our understanding of complex diseases, such as cancer, autoimmune disorders, psychiatric disorders and neurological diseases. Since monozygotic twins are genetic clones (genetically identical), they are considered as perfect models for studying the role of environmental factors as determinants of complex diseases and phenotypes. In this review, a number of intrauterine effects and genetic mechanisms that may affect phenotypic, genotypic, and epigenetic differences between monozygotic twins were described and effects of epigenetic mechanisms on complex diseases were mentioned. Further work on epigenetic changes in diseases using incompatible monozygotic twin models, would lead to new developments in medical therapies.

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“…Псориаз, как известно, имеет сильный генети-ческий компонент с предполагаемой наследуемо-стью 66% [3]. В проявлении патологии задействова-ны большие группы взаимодействующих генов с измененной экспрессией [4][5][6], изменение опреде-ленных участков хромосом (CNVs), локусы, ассоци-ированные с псориазом [7][8][9].…”

Section: Abstract: Psoriasis Epigenetic Factor Dna Methylation Pasunclassified

A new approach to combined therapy of psoriasis

Соболев¹,

Денисова²,

Korsunskaya³

et al. 2015

Klin. dermatol. venerol.

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Псориаз имеет генетический компонент с предполагаемой наследуемостью в 66%. В проявлении патологии задействованы большие группы взаимодействующих генов с измененной экспрессией, аберрация определенных участков хромосом (CNVs), локусы, ассоциированные с псориазом. Однако запуск патологического процесса осуществляется не только совокупным эффектом перечисленных генетических факторов, но и внешними триггерами и эпигенетическими факторами. Важным звеном эпигенетической регуляции является метилирование ДНК. Так, экспериментально установленная определяющая роль метилирования генов в развитии псориаза позволяет расширить круг фармакологи-ческих препаратов, способствующих подавлению псориатических проявлений, за счет включения в их число препаратов, задействованных в реакции трансметилирования. Одним из таких препаратов является адеметионин (Гептрал), способный восполнять дефицит S-аденозил-L-метионина (адеметионина) и стимулировать его выработку в организме. Материал и методы. Под наблюдением находились 253 пациента, страдающих разными клиническими формами псориаза. Обследование пациентов включало общеклиническое исследование, дерматологический осмотр и оценку PASI, определение биохимических параметров крови, клинических лабораторных показателей крови, общеклиническое исследование мочи, рентгенологическое исследование. Пациенты с признаками печеночной патологии были разделены на две группы: больные 1-й группы в качестве гепатопротектора получали препарат Гептрал, 2-й группы -эссенциале Н форте. Результаты. В группе, получавшей Гептрал, все биохимические показатели крови снизились практически до нормальных значений с уменьшением индекса PASI в 4,2 раза. В группе, получавшей эссенциале форте Н, уровни аминотрансфераз (АСТ и АЛТ) оставались все еще значительно повышенными с уменьшением индекса PASI лишь в 3 раза. Оценка дерматологического индекса качества жизни (ДИКЖ) после проведенной терапии продемонстрировала рост среднего балла с 15,6 до 37,2 у пациентов 1-й группы и с 16,1 до 29,8 -во 2-й. Выводы. Проведенное исследование показало высокую эффективность действия Гептрала не только на биохимические показатели крови (АЛТ, АСТ, общий билирубин и другие), но и способствовало положительной динамике клинической картины. Ключевые слова: псориаз, эпигенетический фактор, метилирование ДНК, индексы PASI, ДИКЖ, лечение, адеметионин, Гептрал.Psoriasis is known to have a genetic component with estimated heritability of 66%. Large groups of interacting genes with altered expression, aberration of certain chromosomal areas (CNVs), and loci associated with psoriasis are involved in the pathology manifestation. However, the pathological process is triggered not only by the cumulative effect of these genetic factors but also by external triggers and epigenetic factors. DNA methylation is an important element of the epigenetic regulation. For example, the experimentally established decisive role of gene methylation in the development of psoriasis broadens the range of pharmacological agents, which contribute to the suppression of psoria...

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Psoriasis in Norwegian twins: contribution of genetic and environmental effects

Abstract: High heritability due to additive genetic effects together with considerable environmental contribution to the liability of psoriasis support the current opinion on the multifactorial aetiology of the disease. No sex-specific patterns of heritability of psoriasis were found.

Cited by 78 publications

References 29 publications

Epigenetic Downregulation of SFRP4 Contributes to Epidermal Hyperplasia in Psoriasis

Epigenetic Downregulation of SFRP4 Contributes to Epidermal Hyperplasia in Psoriasis

Epigenetic Basis of Twin Discordance in Diseases: Future Benefits

A new approach to combined therapy of psoriasis

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