Department of Immunology & Molecular Medicine, SKIMS, Srinagar 190011, India.
Department of Immunology & Molecular Medicine, SKIMS, Srinagar 190011, India.
Immunobiology. 2022 May;227(3):152214. doi: 10.1016/j.imbio.2022.152214. Epub 2022 Apr 15.
The etiopathogenesis of AD is multifactorial and defects of the skin barrier, which physiologically constitutes the natural protection, are associated with the disease phenotype. The identification of the genetic and environmental factors paving the way for impaired barrier function is therefore important in developing new therapeutic and prevention strategies.
Confirmed 100 cases were tested against 106 controls for filaggrin mutation and LELP-1 polymorphism by PCR-RFLP and chain termination sequencing. Total IgE and Vitamin D were estimated by ELISA. House dust mite sensitization was assessed by an in-vivo skin prick test.
FLG deletion (2282del4) was present in 4% of the patients and all these were heterozygous carriers, whereas FLG null mutation (R501X) was not present in any of the cases. In the control group, both the mutations were not found. CT genotype and T allele of LELP-1 (rs7534334) were significantly associated with elevated IgE levels, early-onset, HDM sensitization, and disease severity (P < 0.05). However, the genotypic and allelic distribution of LELP-1 among the cases and controls was found to be insignificant.
The low frequency of 2282del4 deletion and the absence of R501X mutation suggest that filaggrin deficiency does not confer a major risk for AD in the Indian population. However, significant association of LELP-1 (rs7534334) variant allele with clinical variables may serve as a novel biomarker for the severity of Atopic Dermatitis as well as an indicator for the allergen-specific immunotherapy and hence bears important clinical implications and needs to study on larger sample size and diverse populations.
探讨特应性皮炎（AD）患者皮肤丝聚蛋白（FLG）缺失突变和白细胞介素 1 受体拮抗剂样蛋白 1（LELP-1）基因多态性与临床表型的相关性。
选取 100 例 AD 患者和 106 例健康对照，采用 PCR-RFLP 和测序法检测 FLG 缺失突变（2282del4）和无义突变（R501X），酶联免疫吸附法（ELISA）检测血清总 IgE 和维生素 D，皮肤点刺试验检测屋尘螨致敏情况，分析 FLG 缺失突变和 LELP-1 基因多态性与 AD 临床表型的相关性。
FLG 缺失突变（2282del4）在 AD 患者中的检出率为 4%（4/100），均为杂合子，而 R501X 突变在 AD 患者和健康对照中均未检出。LELP-1 基因 CT 基因型和 T 等位基因与血清总 IgE 水平升高、早发、屋尘螨致敏和疾病严重程度相关（P<0.05）。但该基因多态性在 AD 患者和健康对照中的分布无统计学差异。
FLG 缺失突变（2282del4）在印度 AD 患者中的检出率较低，提示其可能不是 AD 的主要易感因素。然而，LELP-1 （rs7534334）基因多态性与 AD 临床表型密切相关，可能成为 AD 严重程度的新型生物标志物，对变应原特异性免疫治疗具有一定的指导意义，但其具体作用机制尚待进一步研究。
