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No association of SNP 313A→G in GSTP1 with nephropathy, hypertension and dyslipidemia in type 2 diabetes mellitus.

S. Abbas,Syed Tasleem Raza,S. S Mir,Z. Siddiqi,F. Mahdi

Published 2019 in British Journal of Biomedical Science

ABSTRACT

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycaemia resulting from the combination of resistance to insulin action, excessive or inappropriate glucagon secretion, and inadequate insulin secretion. Prevalence is increasing globally and has reached epidemic proportions in many countries. The number of people living with diabetes is expected to be 592 million by 2035 [1]. Chronic hyperglycaemia without proper management can lead to various shortterm and long-term complications, which may be the main cause of mortality and morbidity. Currently, integrated diabetes care programs focus on diabetesrelated comorbidities such as cardiovascular diseases, retinopathy, nephropathy and diabetic foot [2]. Diabetes is the leading cause of end-stage renal disease, chronic haemodialysis and renal transplantation worldwide. Diabetes-associated nephropathy is a progressive disorder of the microvasculature of the kidney. Microalbuminuria is common among adolescents with T2DM, occurring in 14–22% [3], and hypertension is more prevalent in patients with diabetes than in the non-diabetic population. At least 67% of persons with T2DM either have uncontrolled hypertension or are being treated for elevated blood pressure [4]. Hypertriglyceridemia and low HDL-cholesterol are more common in the diabetic population. Several studies, such as [5], have identified polymorphisms in certain genes that have roles in the complications of diabetes. Hyperglycaemia induces overproduction of reactive oxygen species (ROS) resulting from oxidative stress, one of several mechanisms that contribute in the pathogenesis of T2DM and its related vascular complications through an imbalance between pro-oxidants and antioxidant defence systems. Glutathione S transferase (GST), an endogenous antioxidant, catalyses the conjugation of glutathione to a wide range of exogenous and endogenous hydrophobic electrophiles and so represents a protective mechanism against oxidative stress [6]. GST enzymes participate in destroying free radicals and ROS and act as a defence system [7]. A single nucleotide substitution (SNP, 313A→G) in GSTP1 replacing isoleucine with valine substantially reduces enzymatic activity. Oxidative stresses due to decreased enzyme activity contribute to the destruction of β-cell, an important factor in the development of T2DM [8]. We hypothesized a link between this GSTP1 SNP and the three major clinical complications of diabetes. We recruited 370 T2DM subjects, of whom 122 had Nephropathy (DN), 119 had Hypertension (DH), 129 had Dyslipidemia (DD), and 120 controls from the Diabetic clinic of the Department of Medicine at Era’s Lucknow Medical College & Hospital, Lucknow. Clinical variables including age, sex, blood pressure, Hb A1C (%), lipid profile, etc., were collected. Written informed consent was taken from all participants. Patients with overnight fasting plasma glucose of more than 6.99 mmol/L on two consecutive events were included in T2DM category. T2DM cases with 24h urine albumin excretion rate of 30–300 mg/day (microalbuminuria) and >300 mg/day (macroalbuminuria) were included as diabetic nephropathy cases. T2DM cases with a mean systolic blood pressure (SBP) of >140 mmHg and mean diastolic blood pressure (DBP) of >90 mmHg or taking antihypertensive medications were included as diabetic hypertensive cases. T2DM cases with one or more abnormal lipid values (total cholesterol [TC], LDL and triglycerides [TG]) or HDL-cholesterol, alone or in combination were included in diabetic dyslipidemia cases. Control samples were defined as those with fasting blood sugar level below 6.99 mmol/l without family history of diabetes and its complication and none of them were receiving any medications at the time of participation. Patients suffering from type 1 diabetes, gestational diabetes, maturity-onset diabetes of the young and proved cases of coronary artery diseases and stroke were excluded. The project (Ref no.ELMC/ R-Cell/EC/2014/100) was approved by the Ethics

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