The association between immunogenetics and genetic susceptibility of psoriasis in Thai population

Abstract

Psoriasis is T-cell-mediated skin autoimmunity, required environmental triggers and genetic susceptibility factors to become manifested. Psoriasis is a chronic skin disease characterized by the abnormal hyperproliferation and differentiation of the epidermis, elongated and prominent blood vessels and a thick perivascular lymphocytic infiltrate. Vascular endothelial growth factor (VEGF) gene play important role in pathogenesis of various diseases with angiogenic basis such as breast cancer and autoimmune disease including psoriasis. Many studies analyzed the association of VEGF gene polymorphism in many positions in Caucasian and non-Caucasian. Most reports in some position that really point to important about single nucleotide polymorphism (SNP) with several autoimmune diseases including psoriasis. Although the precise causes of this auto-immune disease remain elusive. It appears to be influenced by stress. The serotonergic system known to depend primarily on the serotonin transporter (5-HTT) may have a role in psoriasis. The serotonin transporter-linked promoter region (5-HTTLPR) polymorphism occurred by insertion/deletion is evident to result in three different length alleles namely S, L as predominant variant alleles and XL as a rare one. These three alleles have 14, 16 and 18 or 20 repetitive DNA sequences, respectively and have been shown to associate with certain neuropsychiatric diseases. Although roles of serotonin and serotonin receptors in psoriasis were investigated, the impact of 5-HTTLPR on psoriasis has not been studied. Therefore, the 5-HTTLPR polymorphism was analyzed to assess whether these variants are associated with psoriasis. Furthermore, having recognized the relationship between oxidative stress and psoriasis, the association between G82S polymorphism in the gene encoding the receptor for advanced glycation end products (RAGE) and psoriasis was investigated. The aims of study, we determine the distribution of VEGF, RAGE and 5-HTTLPR polymorphism in Thai psoriasis patients. We analyzed SNPs within the VEGF (-1557) (C/A), -460(C/T) and +405(C/G)). G82S RAGE and 5-HTTLPR (S, L and XL) gene polymorphism. In population-based case-control study, allele and genotype frequencies of each marker were compared between 234 unrelated healthy volunteers and 154 chronic plapue psoriasis patients (102 early-onset and 52 late-onset psoriasis) for VEGF gene, one hundred seventy eight healthy donors and 134 psoriasis patients for RAGE gene and one hundred twenty seven healthy controls and 142 psoriasis patients for 5-HTTLPR gene. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR-sequence specific primer (PCR-SSP) methods. The results, The -460 TT or CT compared to CC VEGF genotype were found to be significantly risk associated with early-onset psoriasis patients compared with healthy controls (p=0.0450, odds ratio (OR) =4.67, 95% confidence interval (CI) = 1.03-29.52). Interesthingly, haplotype analysis revealed that the CTG haplotype was found to be significantly associated with susceptibility to psoriasis and early-onset psoriasis compared with healthy controls (p=0.0460, OR=1.37, 95% CI=1.00-1.87, p=0.0163, OR=1.54, 95% CI=1.08-2.18, respectively). Moreover, VEGF plasma concentration was not significantly different between groups of haplotype in psoriasis patients. A significantly greater 82A G82S RAGE allele frequency was observed in psoriatic patients than in control subjects (p=0.001 OR=0.52 95% CI=0.35-0.78). Finally, the 5HTTPR polymorphism was no significant change in the allelic frequencies between psoriatic and control subjects (p=0.531, OR=1.15, 95% CI=0.78-1.70). Thus, the result demonstrated that the CTG haplotype and -460 C/T VEGF polymorphism may be used as a genetic marker for early-onset psoriasis in Thais but the 5-HTTLPR was not associated with psoriasis in Thai population. Furthermore, the G82S RAGE polymorphism was associated with psoriasis, and further investigations should be carried out to gain insights into its molecular mechanism in psoriasis.