In the current study homozygosity

In the current study homozygosity for the ACE I allele did not reveal any difference among patients and controls. While, interestingly homozygous D genotype was significantly different among cases and controls, the odds ratio 1.93 revealed D allele to increase the risk of development of psoriasis in the patients. As, it has been reported previously that elevated frequency of II genotype can reduce the inactivation of bradykinin (Murphey et al., 2000). ACE is involved in the degradation of an intricate neuropeptide known as SP, a member of tacykinin family; it increases the vasodilation and vascular permeability. This in turns upregulates the expression of intercellular adhesion molecule-1 (ICAM-1) on human dermal microvascular endothelial Roxithromycin and stimulates the proliferation of human T lymphocytes, which enhances the expression of pro inflammatory cytokines (Kanda and Watanabe, 2002, Maggi, 1997, Quinlan et al., 1998). These phenomena contribute to the development of psoriatic lesions (Nickoloff and Nestle, 2004). (Chang et al., 2007) have demonstrated in their study that homozygotes for D had the highest levels of serum ACE, which can lead to its enhanced activity i.e. degradation of the bradykinin and SP, resulting in increase of the inflammatory responses. Hence, results of the current study seem to indicate that both the homozygotes and heterozygotes for the D allele could have elevated serum activity of ACE and thus they have interrupt the inflammatory activities, which can lead to the manifestation of the psoriasis in patients. The gene encoding eNOS is located on chromosome 7q35–36. The eNOS 4a/b polymorphism of the 27-bp VNTR in intron 4 has 2 common alleles: 4a with 4 repeats (GAAGTCTAGACCTGCTGC (A/G)GGGGTGAG) and 4b with 5 repeats (Thameem et al., 2008). VNTR 4a/b polymorphism role needs further elucidation; it is suggested to regulate the expression of eNOS by the formation of small RNAs (sirRNAs). Endothelial cells containing five copies present higher quantities of sirRNA and lower levels of mRNA of eNOS, when compared with cells that contain four copies (Silva et al., 2011). NO participates in neurotransmission, endothelial vasodilatation, immunity and carcinogenesis. It is synthesized by NOS enzyme family: endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) (Ramirez-Patino et al., 2013). Furthermore, it also maintains the basal vascular tone as well as involve in many other processes such as neurotransmission, vasodilatation, keratinocyte proliferation and apoptosis (Yang et al., 2015). NO is also believed to be involved in stress physiology and stress-related disease processes. Stress has been considered to be a major contributor towards the autoimmune diseases, it also works in producing inflammation and infection via NO pathway (Esch et al., 2002). It has been observed in our results that patients carrying risk allele “a” are at the greater risk of developing psoriasis. Same results have been presented by Coto-Segura et al., 2011, in a study conducted on Spanish population where they reported association of VNTR polymorphism among the patients with psoriasis plaques; they observed that the patients with “aa” and “ab” genotypes are more prone to Psoriasis susceptibility than the patients with “bb” genotype (Coto-Segura et al., 2011). eNOS VNTR polymorphism has been found to be associated with different diseases such as Hypertension, aneurysmal subarachnoid hemorrhage, coronary heart disease, sickle cell disease, type II Diabetes mellitus and psoriasis (Coto-Segura et al., 2011, Jemaa et al., 2009, Staalso et al., 2014). There is also accumulating evidence that hypertension, diabetes, and hypercholesterolemia, ischemic cardiac disease are common associated diseases among Psoriasis patient (Garcia-Diez et al., 2008, Namazi, 2003, Neimann et al., 2006).