Impact of genetic polymorphisms on paediatric atopic dermatitis

Abstract

In order to investigate whether polymorphisms of genes encoding some factors of innate and adaptive immunity play a role in the development of, or protection against atopic dermatitis (AD) and condition its severity, we genotyped 33 candidate genes and 47 single nucleotide polymorphisms (SNPs) using Custom TaqMan Array Microfluidic Cards and an ABI 7900HT analyser (Applied Biosystems, Foster City, CA, USA). The study involved 104 children with AD (29 with mild-to-moderate and 75 with severe disease; 42 girls; mean age ± SD, 5.8 ± 3.3 years) and 119 healthy controls (49 girls; mean age, 4.8 ± 3.0 years). IL10-rs1800872T, TG and MBL2-rs500737AG were all significantly more frequent among the children with AD (P = 0.015, P = 0.004 and P = 0.030), whereas IL10-rs1800896C and TC were more frequent in those without AD (P = 0.028 and P = 0.032). The VEGFA-rs2146326A and CTLA4-rs3087243AG SNPs were significantly more frequent in the children with mild/moderate AD than in those with severe AD (P = 0.048 and P = 0.036). IL10-rs1800872T and TG were significantly more frequent in the children with AD and other allergic diseases than in the controls (P = 0.014 and P = 0.007), whereas IL10-rs1800896TC and C were more frequent in the controls than in the children with AD and other allergic diseases (P = 0.0055 and P = 0.0034). These findings show that some of the polymorphisms involved in the immune response are also involved in some aspects of the development and course of AD and, although not conclusive, support the immunological hypothesis of the origin of the inflammatory lesions.

Cytotoxic T-Lymphocyte Antigen–4 Haploinsufficiency Cutaneous Manifestations

“…Atopic dermatitis (AD) is the most commonly described skin comorbidity, with recent reports of vitiligo, psoriasis, and alopecia . Cytotoxic T-lymphocyte antigen−4 variations have been associated with childhood AD and the severity of AD symptoms, and it can be the initial presenting symptom in 2% of patients . Similarly, CTLA-4 variations have been associated with AA in European populations and psoriasis in Eurasian populations .…”

Genetic relationship between IL-10 gene polymorphisms and the risk of clinical atopic dermatitis

“…In 2013, Chen, et al included seven case-control studies [17–19, 21, 32, 34, 35] to perform a meta-analysis of the association between the IL-10 -1082 A/G polymorphism and the risk of atopic dermatitis [23]. In the present study, we collected the available data from diverse sources and finally added another eight new case-control studies [15, 16, 20, 30, 31, 33, 36, 37] to conduct another updated meta-analysis under the genetic models of allele A vs. G, GG vs. AA, AG vs AA, AG + GG vs AA, GG vs AA+AG and carrier A vs. G. Subgroup analyses stratified by ethnicity, country and HWE were also conducted. Our data failed to support the strong genetic link between the IL-10 -1082 A/G SNP and the risk of atopic dermatitis, which is in line with the outcomes of the above meta-analyses.…”

“…Different results regarding the genetic effect of IL-10 polymorphisms on the risk of atopic dermatitis were reported by individual researchers. For example, the IL-10 -1082 A/G polymorphism was reportedly linked to susceptibility to atopic dermatitis in patients from India [15], Italy [16], and the Czech Republic [17]. Nevertheless, the IL-10 -1082 A/G polymorphism was not associated with atopic dermatitis risk in the Korean population [18] or Polish population [19].…”

Genetic polymorphisms and the development of invasive bacterial infections in children

“…[3][4][5][6] It has been reported that excessive serum levels of proinflammatory cytokines can be frequently found in severe infectious diseases. [7][8][9] However, studies specifically planned to evaluate the importance of genetics in conditioning susceptibility to and clinical manifestations of infectious diseases have reported conflicting results for all these genetic variants. Understanding the relationships between genetic variations and susceptibility to infectious diseases provides useful insight into the pathogenesis of infectious diseases and allows for the elucidation of host-pathogen interactions, improving preventive strategies and providing novel therapeutic approaches.…”

“…3 –6 It has been reported that excessive serum levels of pro-inflammatory cytokines can be frequently found in severe infectious diseases. 7 –9…”