HLA Ⅱ类基因 DRB4*01:01、DRB1*07:01 和 DQB1*03:03:2 对伊朗人群白癜风病临床特征的贡献。

Contribution of HLA class II genes, DRB4*01:01, DRB1*07:01, and DQB1*03:03:2 to clinical features of Vitiligo disease in Iranian population.

机构信息

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, No. Poursina Ave, Tehran, Iran.

Department of Dermatology, Imam Khomeini Hospital Complex, Tehran University of Medical Science, Tehran, Iran.

出版信息

Mol Biol Rep. 2022 Jan;49(1):171-178. doi: 10.1007/s11033-021-06855-3. Epub 2021 Oct 22.

Abstract

BACKGROUND

Vitiligo is a multifactorial depigmentation condition, which is due to skin melanocyte destruction. Increased expression of HLA class II genes in patients with pre-lesions of Vitiligo suggests a crucial role for the participation of immune response in Vitiligo development. Recent studies progressively focused on HLA-DRB1 and DQB1 genes. In this study, we have evaluated the association and role of HLA-DRB401:01, -DRB107:01, and -DQB1*03:03:2 genes in different clinical subtypes of Vitiligo in the Iranian population.

METHODS

First, Genomic DNA from peripheral blood of 125 unrelated Vitiligo patients and 100 unrelated healthy controls were extracted through the salting-out method. Then, HLA class II genotyping was performed using the sequence-specific primer PCR method. Finally, the clinical relevance of the testing for these genotypes was evaluated by applying the PcPPV (prevalence-corrected positive predictive value) formula.

RESULTS

Our results indicated the positive associations of DRB401:01 and DRB107:01 allelic genes with early-onset Vitiligo (p = 0.024 and 0.022, respectively). DRB401:01 also showed strong protection against late-onset Vitiligo (p = 0.0016, RR = 0.360). Moreover, our data revealed that the DRB107:01 increases the susceptibility to Sporadic Vitiligo (p = 0.030, RR = 1.702). Furthermore, our findings proposed that elevated vulnerability of Vitiligo patients due to DRB401:01 and DRB107:01 alleles maybe is correlated with the presence of amino acid Arginine at position 71 at pocket 4 on the antigen-binding site of the HLA-DRB1 receptor.

CONCLUSION

Our findings on different subtypes of Vitiligo suggest that, despite a more apparent autoimmune involvement, a non-autoimmune nature for the etiology of Vitiligo should also be considered.

摘要

背景

白癜风是一种多因素的色素减退病,是由于皮肤黑素细胞破坏所致。白癜风皮损前患者 HLA Ⅱ类基因表达增加,表明免疫反应在白癜风发病中起关键作用。最近的研究逐渐集中在 HLA-DRB1 和 DQB1 基因上。在这项研究中,我们评估了 HLA-DRB401:01、-DRB107:01 和 -DQB1*03:03:2 基因在伊朗人群不同临床亚型白癜风中的关联和作用。

方法

首先,通过盐析法从 125 例无关白癜风患者和 100 例无关健康对照者的外周血中提取基因组 DNA。然后,采用序列特异性引物 PCR 法进行 HLA Ⅱ类基因分型。最后,应用 PcPPV(校正阳性预测值)公式评估这些基因型检测的临床相关性。

结果

我们的结果表明,DRB401:01 和 DRB107:01 等位基因与早发性白癜风呈正相关(分别为 p=0.024 和 0.022)。DRB401:01 对迟发性白癜风也有很强的保护作用(p=0.0016,RR=0.360)。此外,我们的数据表明,DRB107:01 增加了散发型白癜风的易感性(p=0.030,RR=1.702)。此外,我们的研究结果表明,由于 HLA-DRB1 受体抗原结合部位口袋 4 上的第 71 位氨基酸精氨酸的存在,DRB401:01 和 DRB107:01 等位基因使白癜风患者的易感性增加。

结论

我们对不同亚型白癜风的研究结果表明,尽管有更明显的自身免疫参与,但也应考虑白癜风病因的非自身免疫性质。

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