The response of acromegalic patients (Diabetic versus non-diabetic) to Long - acting - repeatable Octreotide (LAR) in the presence or absence of Glutathion S transferase (GSTM1,GSTT1) Genes

• Published in: Journal of pharmaceutical sciences and research Vol. 10; no. 12; p. 3090
• Main Authors: Hameed, Areej Sh, Khaleel, Fayhaa M, Rahma, Abbas M
• Format: Journal Article
• Language: English
• Published: Cuddalore Journal of Pharmaceutical Sciences and Research 01.12.2018
• Subjects: Age; Breast cancer; Cardiovascular disease; Clinical medicine; Colorectal cancer; Deoxyribonucleic acid; Diabetes; Diabetic retinopathy; Disease control; DNA; Endocrinology; Enzymes; Genes; Growth hormones; Medical research; Metabolism; Patients; Tumors; Iraq
• ISSN: 0975-1459

Comorbidities as hypertension and diabetes are common among acromegalic subjects(8,9)Glutathione S-transferases (GSTs) constitute multifunctional enzymesthat are coded by at least eight distinct loci: a (GSTA), p (GSTM),0 (GSTT), n (GSTP), a (GSTS), κ (GSTK),i?(GSTO), and Ç (GSTZ), each onecomposed by one or more homodimeric or heterodimeric isoforms(8,9).These enzymes are involved in the conjugation reactions duringphase II of the xenobiotic metabolism, catalyzing reactions betweenglutathione (GSH) and a variety of potentially toxic and carcinogenicelectrophilic compounds (10,11), besides, GSTs also display peroxidaseactivity and can thus protect from oxidative damage (12) The deficiencyin the activity of this enzyme can be derived from the inheritedGSTs polymorphisms, e.g., GSTT1 (22q11.23), GSTM1 (1q13.3) (13).These genes were studies in all enrolled patients to find out the impact of presence of such gene on the response of our enrolled patients to octreotide LAR ,injections .The enrolled subjects are subdivided to diabetic and nondiabetic. The study was designed in a way to detect any relation between those harboring GSTM1 or GSTT1 or both to control of their disease in the presence or absence of diabetes.The gold standard therapy is trans - sphenoidal hypophysectomy ,however it is not the only modality as patient have to be treated individually keeping in mind the role of medical treatment with somatostatin analogues as octreotide LAR or Lanreotide and there is a role for gamma-knife radio surgery in some patients.The main problem which is faced by the physician is selction of the ideal modality of treatment in order to achieve the three goals which are :reduction of the adenoma size if its removal is not fcosible ,reduction of IGF-1 to the age and sex matched control and reduction of GH to <1 ng/ml that marks cure or < 2.5 ng/ml that marks disease control MATERIAL AND METHODS Subjects and Sample Collection In the National Diabetic Center (NDC) ,more than 250 acromegalic patients are registered and followed up for variable time but the registry starts in 2004. To compare the current study with others a comparable study is not available after on extensive search in the literature however the impact of presence of GSTM1 or GSTT1 have been studied to find out its association with diabetes in North India(18).They observed presence association of GSTM1 genotype with type 2DM so GSTM1 gene polymorphism may be predictive marker of type 2 DM(18).The relation of these genes have been studied to fixed out any sussceptibility to astrocytoma and meningioma ,polymorphism in these genes encodes for carcinogen metabolizing enzymes thus having an unfavorable effect by increasing the risk to develop astrocytoma and meningloma thus there are on going studies to find out any detoxifying agent that can reduse the chance of development of thus tumors. (19)Lee et al. has found an association between GSTM1,GSTT1 and GSTP1 polymorphism and the risk of advanced colorectal cancer in smokers and non smokers, as smoking is known risk factor for colorectal adenoma and Glutathion S transferase can detoxify such carcinogens in tobacco smoke.GSTM1 inactive allels reduce the chance of Colorectal Cancer while having inactive GSTT1 allel was found to increase the risk of Colorectal Cancer among smokers only(19).The relation of these genes with breast cancer have been studied in Iraq to find out the impact of GSTP1 gene polymorphism on cancer of the breast.