Dataset Information

Association Study of the Caspase Gene Family and Psoriasis Vulgaris Susceptibility in Northeastern China.

ABSTRACT: Background:Abnormal apoptosis of keratinocytes is one of the pathological changes of psoriasis. Caspases (CASPs) are the central engines of apoptosis. Studies to date have shown that some SNPs alter the expression of related genes and lead to changes in disease risk. However, no studies have investigated the associations between gene polymorphisms and the risk of psoriasis in Han population in northeast China. Therefore, we conducted a case-control study to explore this question in Han population of northeastern China. Methods:540 patients with PsV and 612 healthy age- and sex-matched controls were enrolled in this study. We determined the genotypes of 17 single nucleotide polymorphisms (SNPs) from 11 genes of caspase family by the improved multiplex ligation detection reaction (iMLDR) method. A model-based single SNP frequentist test and haplotype association studies were performed to evaluate the association between SNPs and PsV. Results:In the single SNP tests, rs6704688 in CASP8 was significantly associated with psoriasis vulgaris (PsV) in Han population of northeastern China (P = 0.0169, P' = 0.0179 under the additive model; P = 0.0126, P' = 0.0149 under the heterozygous model). In haplotype analyses, the CASP7 haplotype GC was found to be associated with PsV risk (case group versus control group, 47.2% versus 54.4%, respectively, p = 0.0149). Conclusions:Our study presented that the gene polymorphisms of CASP7 and CASP8 were significantly associated with PsV in Han population of northeastern China, which implied the functional relationship between PsV and caspase genes. CASP8 and CASP7 SNPs could be new potential biomarkers for risk stratification and prevention of PsV.

SUBMITTER: Yao X

PROVIDER: S-EPMC6398065 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association Study of the Caspase Gene Family and Psoriasis Vulgaris Susceptibility in Northeastern China.

Yao Xinyu X Hao Siyu S Yu Pei P

BioMed research international 20190217

<h4>Background</h4>Abnormal apoptosis of keratinocytes is one of the pathological changes of psoriasis. Caspases (CASPs) are the central engines of apoptosis. Studies to date have shown that some SNPs alter the expression of related genes and lead to changes in disease risk. However, no studies have investigated the associations between gene polymorphisms and the risk of psoriasis in Han population in northeast China. Therefore, we conducted a case-control study to explore this question in Han p ...[more]

PMID: 30906769

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Project description:BackgroundPsoriasis is an incurable, chronic skin disorder with considerable impact on the quality of life. No drugs are available for treating the disease. Clarifying the progression, exploring the risk factors affecting progression, and finding effective treatments with few side-effects and low recurrence rates is critical. This protocol describes a future study that will analyze psoriasis vulgaris progression risk factors and trends, establish a multicenter clinical registration platform, evaluate clinical evidence for Chinese Medicine (CM) intervention for psoriasis, and evaluate therapeutic effectiveness and recurrence rate advantages of CM.MethodsThe study is a prospective cohort clinical trial planned for October 2019 to September 2021 involving 20 clinics. The trial will enroll 1,500 participants in a psoriasis vulgaris group, and 500 healthy participants in a control group (no intervention). The psoriasis vulgaris group will be divided into three equal-sized subgroups: blood heat syndrome group (BHS), blood stasis syndrome group (BSS), and non-blood heat nor blood stasis syndrome group (NHS) group. Participants will be grouped according to CM syndrome classification and receive oral CM herbal medication (according to the CM syndrome classification, and tailored to the participant's disease progression). Medication will be administered twice every day during the intervention phase (eight weeks of intervention, and eight weeks of follow-up). Exposure measures include demographic variables, risk factors, and intervention factors.DiscussionThe primary outcome measures include improvement in both the psoriasis and severity index scores after eight weeks of intervention. Secondary outcome measures include body surface area affected, Physician Global Assessment scores, Dermatology Life Quality Index, pain-relat ed quality of life, pain on visual analog scale, CM syndromes, and recurrence. Other outcome measures include CM physical scale, personal history, medical expenses, and patient satisfaction. The number, nature, and severity of adverse events will be carefully recorded.Trial registrationThe trial has been registered at ClinicalTrials.gov (ID: NCT03942185).

Project description:BackgroundThe association between psoriasis vulgaris and bullous pemphigoid (BP) remains largely unknown.ObjectivesTo investigate whether there is a causal effect between psoriasis vulgaris and BP.MethodsTwo-sample bidirectional Mendelian randomization (MR) analyses were conducted using publicly released genome-wide association studies (GWAS) summary statistics. The GWAS summary statistics for BP were downloaded online from FinnGen Biobank Documentation of the R12 release, which includes 219 BP cases and 218,066 controls. The GWAS data for psoriasis vulgaris were extracted from Sakaue et al., which comprises 5072 cases and 478,102 controls. Single-nucleotide polymorphisms (SNPs) associated with exposure were selected as instrumental variables by performing additional quality control steps. The inverse-variance-weighted (IVW) method was used for the primary MR analyses, and the MR-Egger regression, weighted mode method, weighted median method, and simple mode were employed for sensitivity analyses. The MR-Egger intercept test and "leave-one-out" sensitivity analysis were performed to evaluate the horizontal pleiotropy and the potentially influential SNPs, respectively.ResultsGenetically determined log odds of psoriasis vulgaris were associated with an increased risk of BP (IVW: odds ratio (OR) = 1.263, 95% confidence interval (CI): 1.013-1.575, P=0.038). Sensitivity analyses by the weighted mode (OR=1.255, 95%CI: 0.973-1.618, P=0.106), MR Egger (OR=1.315, 95%CI: 0.951-1.817, P=0.126), simple mode (OR=1.414, 95%CI: 0.823-2.429, P=0.234) and weighted median method (OR=1.177, 95%CI: 0.889-1.559, P=0.254) derived directionally consistent relationship between the genetically predicted log odds of psoriasis vulgaris and risks of developing BP. On the contrary, we found that genetically predicted BP had no significant effect on psoriasis vulgaris (IVW: OR=0.996, P= 0.707), indicating the unidirectionality of the relationship. MR-Egger intercept tests showed no evidence of horizontal pleiotropy. No influential SNP driving the results was detected by the leave-one-out sensitivity analysis.ConclusionsOur results suggested that psoriasis vulgaris causally increases the risk of BP, highlighting the need for potential strategies for the prevention and early diagnosis of comorbid BP in patients with psoriasis vulgaris. Further researches into this association and underlying mechanisms are warranted.

Dataset Information

Association Study of the Caspase Gene Family and Psoriasis Vulgaris Susceptibility in Northeastern China.

Publications

Association Study of the Caspase Gene Family and Psoriasis Vulgaris Susceptibility in Northeastern China.

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