TNFAIP3 and IL12B gene polymorphisms associated with psoriasis vulgaris in an Egyptian cohort.

BACKGROUND: Psoriasis vulgaris is a common chronic inflammatory skin disease. Development of early onset psoriasis is, to some extent, genetically determined and a strong association with the major histocompatibility complex HLA-Cw6 has been demonstrated. The use of genome-wide association studies has highlighted novel genes associated with the development of psoriasis as IL12B, IL23R, TNFAIP3 and IL13 for instance. The majority of these studies were performed on cohorts of European descent. OBJECTIVE: To determine whether inter-ethnic differences exist in the genetic susceptibility to psoriasis, we genotyped single-nucleotide polymorphism variations in the vicinity of candidate genes in 132 Egyptian patients and 175 healthy controls. METHODS: Blood samples of patients and controls were screened for nucleotide polymorphisms in four candidate genes by TaqMan single-nucleotide polymorphisms Genotyping Assays. RESULTS: We found a significant association between psoriasis and the single-nucleotide polymorphism rs610604, within the TNFAIP3 gene. The TNFAIP3 gene is involved in the TNF-α signalling cascade (P-value: 0.004952), a key step in the pathogenesis of psoriasis. Although there was no significant association found between rs610604 (IL12B) and rs11209026 (IL23R) in this population, the interaction of these two genes showed a significant association with psoriasis (P-value: 0.025). Moreover, when selecting the patients with early disease onset (less than 30 years), we also found that the association of IL12B and psoriasis was highly significant (P-value 1.14 × 10(-12)). No association between rs20541 (IL13) and psoriasis was observed in our Egyptian cohort. CONCLUSION: Replicating the association of single-nucleotide polymorphisms in the TNFAIP3, IL12B and IL23R genes with psoriasis vulgaris, in subjects from different ethnic backgrounds, underlines their importance in the pathogenesis of the disease. In contrast, the lack of any association between rs20541 (IL13) and psoriasis in our Egyptian cohort suggests the existence of important inter-ethnic genetic differences in psoriasis susceptibility.

Antioxidant status in children with juvenile rheumatoid arthritis (JRA) living in Cairo, Egypt.

The aim of this study was to examine both enzymatic and non-enzymatic antioxidant status in a select group of children with juvenile rheumatoid arthritis (JRA), living in Cairo, Egypt. The plasma concentrations of albumin, ceruloplasmin, vitamin C, vitamin E as well as erythrocyte superoxide dismutase and whole blood glutathione peroxidase activities were all significantly decreased in the presence of JRA compared to those without JRA. Unlike these antioxidant factors, vitamin A and its carrier (e.g. retinol binding protein), which have very little or no antioxidant property, remained unaffected by JRA. These results suggest that the children with JRA are subject to oxidative stress.

Antioxidant status in children with protein-energy malnutrition (PEM) living in Cairo, Egypt.

OBJECTIVES: Free radicals are implicated in many diseases. The rise in free radicals associated with antioxidant deficiency results in tissue damage. The pathogenesis of oedema and anaemia commonly found in children with protein-energy malnutrition (PEM) has been suggested to be caused by an imbalance between the production of toxic radicals and their safe disposal. The aim of this study was to evaluate antioxidant status in children with PEM. DESIGN: A total of 68 children (age range: 3 months to 3 years) living in Cairo, Egypt were recruited. Forty-six of these subjects had different degrees of PEM; they were admitted at the Abo-Elrish Hospital, Cairo. Of these, 26 children had kwashiorkor (KWO) and twenty had marasmus (MAR). Twenty-two age and sex matched healthy well-nourished children were recruited from the local community, and used as controls. METHODS: The antioxidant status of the study population was determined by measuring copper-zinc superoxide dismutase (Cu-Zn, SOD) in red blood cells, glutathione peroxidase (GPX) in whole blood, and ceruloplasmin in plasma. In addition, the plasma levels of trace-elements involving antioxidant activities, such as copper (Cu), zinc (Zn), and selenium (Se) were determined, along with a select group of vitamins. The latter included vitamin A (retinol), vitamin E (alpha-tocopherol) and vitamin C (ascorbic acid). RESULTS: The mean whole blood GPX activity along with plasma levels of vitamins A, E and C as well as ceruloplasmin, Cu and Se were all lower in children with either KWO or MAR than their corresponding control subjects. The erythrocyte SOD activity, on the other hand, was increased while the plasma Zn concentrations were either increased or not changed in the malnourished children. It was of interest that while haemoglobin concentrations were decreased, the plasma free iron (Fe) levels were significantly increased in children with KWO. CONCLUSIONS: The significant increase in red cell SOD activity associated with the decrease in plasma ceruloplasmin, antioxidant vitamins and the whole blood GPX activity in PEM children suggest that these children are potentially susceptible to high oxidative stress. An elevated plasma Fe concentrations, especially with KWO may augment the harmful effect of free radicals with a clinical consequence of oedema.