METHODS: Gene-based and gene-level meta-analyses were performed on data extracted from our previous study data sets (2,483 patients with guttate psoriasis and 8,292 patients with non-guttate psoriasis) for genotyping. Then, haplotype analysis was performed for rare loss-of-function variants located in MED12L, and protein function prediction was performed for MED12L. Gene-based analysis at each stage had a moderate significance threshold (p < 0.05). A χ2 test was then conducted on the three potential genes, and the merged gene-based analysis was used to confirm the results. We also conducted association analysis and meta-analysis for functional variants located on the identified gene.
RESULTS: Through these gene-level analyses, we determined that MED12L is a guttate psoriasis susceptibility gene (p = 9.99 × 10-5), and the single-nucleotide polymorphism with the strongest association was rs199780529 (p_combine = 1 × 10-3, p_meta = 2 × 10-3).
CONCLUSIONS: In our study, a guttate psoriasis-specific subtype-associated susceptibility gene was confirmed in a Chinese Han population. These findings contribute to a better genetic understanding of different subtypes of psoriasis.
方法:基于基因和基因水平的荟萃分析是从我们以前的研究数据集(2,483例滴状银屑病患者和8,292例非滴状银屑病患者)中提取的数据进行基因分型。然后,对位于MED12L中的罕见功能丧失变体进行单倍型分析,并对MED12L进行蛋白质功能预测。每个阶段的基于基因的分析具有中等显著性阈值(P<0.05)。然后对三个潜在基因进行卡方检验,并使用合并的基于基因的分析来确认结果。我们还对位于鉴定基因上的功能变异进行了关联分析和荟萃分析。
结果:通过这些基因水平分析,我们确定MED12L是点滴状银屑病易感基因(P=9.99x10-5),关联最强的单核苷酸多态性(SNP)是rs199780529(P_combine=1x10-3,P_meta=2x10-3)。
结论:在我们的研究中,在中国汉族人群中证实了点滴状银屑病特异性亚型相关易感基因.这些发现有助于更好地理解银屑病的不同亚型。