Variation at Interleukin-10 Locus Represents Susceptibility to Psoriasis in North Indian Population.

BACKGROUND: IL-10 is an important pleiotropic, immunoregulatory and anti-inflammatory cytokine which plays a significant role in the pathogenesis of psoriasis. OBJECTIVE: The aim of the present study was to determine whether the three polymorphic sites of the IL-10 gene, haplotype and serum level confer susceptibility to psoriasis. METHOD: 200 psoriatic patients and 200 controls were genotyped for three IL-10 polymorphic sites by ARMS polymerase chain reaction. Serum levels of IL -10 were measured by ELISA. RESULTS: Our results demonstrated that polymorphism of IL-10 -592 C/A (adjusted* OR = 9.25; 95% CI =3.16- 27.06) and IL-10 1082 A/G (adjusted* OR = 4.28; (95% CI =1.46- 12.56) was found to be in association with increased risk of psoriasis while as IL- 10 819 C/T (adjusted* OR= 1.60; (95% CI = 0.65-3.95) polymorphism does not show any significant association with the risk of psoriasis. HT7 GTC haplotype is associated with increased risk of psoriasis. Serum levels of IL-10 were found to be significantly low in patients, as compared to controls with a non-significant correlation between serum IL-10 level and psoriasis severity. CONCLUSION: IL-10 polymorphism imparted significant risk towards the development of psoriasis in North Indian population. Highlighting the role of IL-10 cytokine in the pathogenesis of psoriasis will help in the development of psoriasis management.

Role of Angiogenic Growth Factors in Psoriasis: A Review.

BACKGROUND: Psoriasis is a chronic disease of inflammatory nature. It involves autoimmune mechanism and the systemic diseased state is created by the interaction of immune system, autoantigens and variety of environmental triggers. It is a complex skin disease which involves participation of numerous factors, making it multifactorial in nature. The main characteristics include proliferation of keratinocytes, increase in dermal vascularity and infiltrated immune cells. Among all factors, vascular alterations present a significant feature of the disease and angiogenesis seems to have an important role in giving rise to psoriasis phenotype. In the early phases of psoriasis there occurs sprouting of new blood vessels which disappear with disease clearance. Psoriatic lesions show highly altered vascular network in the form of numerous enlarged, tortuous and hyperpermeable cutaneous blood vessels. Secretion of various pro-angiogenic growth factors promote the expansion of vascular network in psoriatic skin cells. In addition to pro-angiogenic growth factors, pro-inflammatory cytokines also contribute to this process by activating endothelial cells and exerting pro-angiogenic action as well. Angiogenesis, in psoriasis display a close association of vascular endothelium activation, angiogenesis, inflammation and lesional skin, as is demonstrated by in vivo models. OBJECTIVE: The present review discusses angiogenesis as the central process in the evolution of psoriasis and summarizes various angiogenic mediators and their respective roles in the development of psoriasis. CONCLUSION: Anti-angiogenic therapies targeting vasoproliferation may represent a valid approach for the development of anti-psoriatic drugs and further development in this field can pave way to new fields of treatment. Such therapies could be at par to those directly targeting inflammation.

Association of genetic polymorphism of interleukin-17A & interleukin-17F with susceptibility of psoriasis.

BACKGROUND & OBJECTIVES: Psoriasis is a chronic inflammatory skin disease with unknown aetiology. So far studies have confirmed that interleukins, pro-inflammatory factors and T-cell activation play major role in the development of disease. Interleukin-17 (IL-17) a T helper inflammatory cytokine, was found to be positively correlated with severity of psoriasis. However, the specific mechanism has not been clarified. IL-17A and IL-17F are group members of IL17 family cytokines and found to be located adjacent to one another on the same human chromosome, 6p12. The present study was designed to identify the association between IL-17A and IL-17F gene polymorphism with susceptibility of psoriasis in north Indian population. METHODS: A total of 166 psoriasis patients and 150 healthy controls were genotyped for IL-17A and IL-17F gene polymorphism by amplification refractory mutation system-polymerase chain reaction method. One single nucleotide polymorphism (SNP) was analysed in IL-17A (rs10484879) and one SNP in IL-17F (rs763780) to look for an association with psoriasis. RESULTS: Our study indicated decreased frequency of IL-17A (rs10484879) G allele (51.8 vs. 65.0%), and IL-17F (rs763780) C allele (36.5 vs. 45.7%) in psoriatic patients as compared to healthy controls. INTERPRETATION & CONCLUSIONS: The present findings suggest that IL-17A (rs10484879) G/T and IL-17F (rs763780) C/T gene polymorphisms may contribute in pathogenesis of psoriasis. Further studies need to be done to confirm these findings.

Serum leptin levels, leptin receptor gene (LEPR) polymorphism, and the risk of systemic lupus erythematosus in Kashmiri population.

The study is conducted to evaluate relationship between LEPRQ223R (Gln > Arg) polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG + GG) in cases compared to controls [OR = 2.52, CI = 1.18-5.35, p = 0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR = 1.49, p = 0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR = 11.8, CI = 1.6-85.1, p = 0.002] and an inverse association with cardiac disorder [OR = 0.09, CI = 0.02-0.46, p = 0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9 ± 19.5 vs 14.8 ± 10.4, p < 0.001). SLE patients in the highest quartile leptin levels (≥32.5 ng/mL) were significantly more likely to have higher BMI (p = 0.001) and increased risk of developing arthritis (p = 0.02). Furthermore positive association was observed between the variant genotype(AG + GG) and leptin levels (p = 0.001) in SLE patients. Thus, it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.

RAD51 G135C gene polymorphism and risk of colorectal cancer in Kashmir.

RAD51 - a DNA double-strand breaks repair gene plays an important role in homologous recombination, a process frequently involved in cancer transformation. The aim of this study was to compare the distribution of the genotype of the RAD51 G135C polymorphism between colorectal cancer (CRC) patients and controls. We also tested the association between the G135C polymorphism of the RAD51 gene and the risk of CRC, and various clinicopathological parameters. Polymorphism was evaluated by restriction fragment length polymorphism PCR in 100 CRC patients and 120 age-matched and sex-matched controls. There was a significant association between RAD51 genotypes and CRC cases (P<0.05). Also, the GC genotype was associated with an increased risk of CRC (odds ratio >3.84). Our results suggest that the G135C polymorphism of the RAD51 gene is associated with an increased risk of CRC in our population.