Archives

  • 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • ACE also known as Kininase II is an

    2019-11-06

    ACE also known as Kininase II is an important enzyme of the Renin angiotensin LY 2157299 synthesis system (RAAS) (Novo et al., 1987), it is believed to be a potent blood pressure regulator and also plays a crucial role in activation of the bradykinin receptor via inactivation of bradykinin which works to induce the symptoms of vasodilation, inflammation, pain and plasma extravasation (Hooper, 1991, Szyszymar and Wachowska, 1975). A 287-base pair repetitive sequence in intron 16 of the ACE results in insertion/deletion (I/D) polymorphism leading to the advent of variable serum ACE concentration (Rigat et al., 1990). It has been observed that treatment with ACE inhibitors extravagates the symptoms of psoriasis in certain subjects (Wolf et al., 1990). There are many conflicting results reported till now regarding the I/D polymorphism in causing psoriasis (Al-Awadhi et al., 2007, Chang et al., 2007, Ozkur et al., 2004, Weger et al., 2007, Yang et al., 2014). eNOS when present at high levels reported to be associated with formation of psoriatic lesions by promoting the skin microvasculature, keratinocyte differentiation and proliferation (Duan et al., 2016). Nitric oxide (NO) synthesized by eNOS is a potent intercellular messenger as well as cytotoxic effector molecule contributing towards the pathophysiology of various autoimmune diseases including psoriasis through promoting cell differentiation, proliferation and especially apoptosis (Singh et al., 2000). It has been found that eNOS expression is elevated in psoriatic lesions of patients (Ormerod et al., 1998). The 27-bp repeat polymorphism in intron 4 (variable number of tandem repeat) shows two common alleles containing four repeats (a) and five repeats (b), which further produces two homozygous (aa and bb) and one heterozygous (ab) genotypes (Yoon et al., 2000). VNTR (a/b) is considered to be responsible for change in plasma NO concentration by affecting the endothelial NO synthesis hence promoting susceptibility to autoimmune diseases (Bunjevacki et al., 2016). MTHFR is the key enzyme of Homocysteine (Hcy)/methionine metabolism, thus decreased activity of it could result in defective DNA methylation that could be responsible for the aberrant cellular proliferation (Selhub and Miller, 1992). It is assumed that plasma Hcy levels are determined by Folate and vitamin B12 levels thus MTHFR plays a cardinal role in molecular interaction with these molecules (Santos et al., 2011). MTHFR deficiency actually affects the remethylation of homocysteine to methionine (Me); it catalyzes the reduction of methylene-(Tetrahydofolate) THF to Me-THF while Flavin Adenine Dinulcleotide FAD serves a cofactor. The aberrant metabolic cycle due to deficiency of MTHFR has been reported previously to result in severe hyperhomocysteinemia, which can result into neurological abnormalities, mental retardation, as well as autoimmune disorders such as arteriosclerosis, and thrombosis (Engbersen et al., 1995). Results of many studies have shown hyperhomocysteinemia to be the major risk for development of psoriasis plaques in patients with cardiovascular disease (Brazzelli et al., 2010, Malerba et al., 2006). Aberrant utilization of folate due to MTHFR polymorphisms can accelerate the keratinocyte proliferation rate by modulating the DNA turnover rate (Karabacak et al., 2014). There are many conflicting results about the association of MTHFR polymorphisms with the induction or exacerbation of psoriasis in different population (Harmon et al., 1996, Karabacak et al., 2014). However, certain studies reported no role of MTHFR polymorphisms in pathophysiology of psoriasis (Liew et al., 2012). Based on these contradictory reports about ACE, eNOS and MTHFR polymorphisms, the current study is aimed to assess the role of genotype correlation of ACE rs464699, eNOS rs869109213, MTHFR rs22744976, rs1801133 and rs1801131 with the pathophysiology of psoriasis in Pakistani patients.
    Methods Subjects were recruited from the regular medical clinics in the Islamabad Capital Territory and the Punjab province. Patient recruitment was approved by the Ethics Review Board of the Department of Biosciences, COMSATS Institute of Information Technology Islamabad, Pakistan, and adheres to the Declaration of Helsinki. The collected samples consisted of 240 psoriasis cases and 264 healthy controls, all of whom were collected from the same geographic region. Informed consent was obtained from all individual participants included in the study. Diagnosis of psoriasis was performed as part of the routine clinical care by dermatologists, and no attempt was made to classify the study subjects into psoriasis subtypes. Most patients had chronic, non-pruritic lesions showing Auspitz\'s sign. Eighty percent of the patients had type1 psoriasis, with an age at onset ≤40years, as defined by Henseler and Christophers. Control subjects were adults with no history of psoriasis and unrelated to the cases. After obtaining written informed consent, peripheral blood samples were collected by venipuncture, and DNA was prepared by standard organic methods.