Several Proinflammatory Genes' Variability and Phenotypes of Atopic Dermatitis in Czech Adult AD Patients.

BACKGROUND

The etiopathogenesis of atopic dermatitis is complicated, and it includes aspects such as dysfunction of the skin barrier, changes in immune responses, IgE-mediated hypersensitivity, and many characteristics of the environment. Regarding skin barrier dysfunction, a number of genetic changes have been described. This genetic predisposition could be related to the phenotypes of atopic dermatitis.

AIM

In this study, several polymorphisms in five proinflammatory genes were associated with certain phenotypes of AD patients (genotype-phenotype study).

METHODS

In total, 89 unrelated AD Czech (Caucasian) patients were genotyped regarding five proinflammatory gene polymorphisms (angiotensinogen AGT M235T, AGT-6 G/A, TNF-α-238 G/A, TNF-β Fok1, IL-6-174 C/G and IL-6-596 G/A). Genotyping was performed using PCR and restriction analysis. For phenotypes, patients' sex, age and personal and family history of atopy, aero- and food allergies and other complex diseases were evaluated.

RESULTS

A significant association with transepidermal water loss (TEWL) measured on the forearm was found with the AGT M235T polymorphism ( = 0.02). For the AG genotype of TNF-α-238 G/A, a six-times higher risk for a family history of diabetes mellitus compared to other examined aspects of family history was found ( = 0.02). A family history of thyreopathy was associated with the IL-6-174 G/C polymorphism when compared to a family history of other complex diseases. The GG genotype had a ten-times higher risk for a family history of thyreopathy compared to the other genotypes ( = 0.004). This result was highly specific (0.914). The GG genotype of IL-6-596 G/A was associated with a family history of thyreopathy, with the same result ( = 0.004). Moreover, the G allele of IL-6-174 G/C was associated with a family history of thyreopathy compared to AD patients without a positive family history of complex diseases ( = 0.03). In AD men, the MM genotype of the AGT M235T gene was found to be associated with food allergies ( = 0.004). This result was highly sensitive (0.833). A family history of cardiovascular disease in AD men was associated with AGT-6 G/A variability. The A allele was found to be six times more frequent in patients with a positive family history of cardiovascular disease ( = 0.02, with high sensitivity and specificity (0.700 and 0.735, respectively)). A family history of diabetes mellitus was associated with the TNF-β Fok1 polymorphism, where the B1 allele was almost six times more frequent in AD men with a positive family history of diabetes mellitus ( = 0.02), with high sensitivity (0.85). A significant association between TEWL measured on the forearm and the AGT M235T polymorphism was found when AD women were carriers of the MM genotype, with a median of 25 and range 4-61; those patients with the MT genotype had a median of 10 and range of 0.3-39; and patients with the TT genotype had a median of 5 and range of 3-40, = 0.003. The polymorphism AGT-6 G/A was associated with different ages of eczema onset. The AG genotype was almost nine times more risky for the youngest group (0-7 years) compared to the oldest group (more than 18 years) ( = 0.02), with high specificity for this result.

CONCLUSIONS

Our results in the field of cytokine signaling in the immune system in patients with atopic dermatitis are in agreement with those of GWASs. We suggest that cost-effective and simple PCR tests may be the best approach for the rapid and optimal collection of valid genetic information in clinical practice.