Novel Association of WNK4 Gene, Ala589Ser Polymorphism in Essential Hypertension, and Type 2 Diabetes Mellitus in Malaysia

Abstract

With-no-lysine (K) Kinase-4 (WNK4) consisted of unique serine and threonine protein kinases, genetically associated with an autosomal dominant form of hypertension. Argumentative consequences have lately arisen on the association of specific single nucleotide polymorphisms ofWNK4gene and essential hypertension (EHT). The aim of this study was to determine the association of Ala589Ser polymorphism ofWNK4gene with essential hypertensive patients in Malaysia.WNK4gene polymorphism was specified utilizing mutagenically separated polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method in 320 subjects including 163 cases and 157 controls. Close relation betweenAla589Serpolymorphism and elevated systolic and diastolic blood pressure (SBP and DBP) was recognized. Sociodemographic factors including body mass index (BMI), age, the level of fasting blood sugar (FBS), low density lipoprotein (LDL), and triglyceride (TG) in the cases and healthy subjects exhibited strong differences (p<0.05). The distribution of allele frequency and genotype ofWNK4geneAla589Serpolymorphism showed significant differences (p<0.05) between EHT subjects with or without type 2 diabetes mellitus (T2DM) and normotensive subjects, statistically. TheWNK4gene variation influences significantly blood pressure increase.Ala589Serprobably has effects on the enzymic activity leading to enhanced predisposition to the disorder.