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 of WNK4 gene and essential hypertension (EHT). The aim of this study was to determine the association of Ala589Ser polymorphism of WNK4 gene with essential hypertensive patients in Malaysia. WNK4 gene 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 between Ala589Ser polymorphism 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 of WNK4 gene Ala589Ser polymorphism showed significant differences (p < 0.05) between EHT subjects with or without type 2 diabetes mellitus (T2DM) and normotensive subjects, statistically. The WNK4 gene variation influences significantly blood pressure increase. Ala589Ser probably has effects on the enzymic activity leading to enhanced predisposition to the disorder.

Geospatial analysis of type 2 diabetes mellitus and hypertension in South Sulawesi, Indonesia

“…A cumulative genetic risk score consisting of 14 of the 38 SNPs is important for hypertension and increased propensity for systolic blood pressure and may contribute to hypertension in T2DM in this country 10 . Another study conducted in Malaysia involving 320 volunteers classified based on hypertension (163) and normotensive (157) conditions showed that TT genotype/T allele of the WNK4 gene resulted in a close relationship between hypertension and T2DM 11 . While genetic study remained limited in Indonesia, it is been documented that polymorphism of rs87148, especially CC genotype and C allele, and CAPN10 had a significant association with HbA1c level and increased T2DM vulnerability, respectively 12 , 13 .…”

Geospatial Analysis of Diabetes Type 2 and Hypertension in South Sulawesi, Indonesia

“…Another study conducted in Malaysia involving 320 volunteers divided based on hypertension (163) and normotensive (157) groups. The TT genotype/T allele of the WNK4 gene resulted in a close relationship between hypertension and diabetes mellitus 10 .…”

Kidney ion handling genes and their interaction in blood pressure control

“…Except for WNK2, the other members of WNKs family have been reported to be associated with blood pressure or hypertension. A lot of blood pressure-associated polymorphisms of WNKs have been identified, including rs1468326 [ 96 ], rs765250 [ 97 ], rs880054 [ 98 , 99 ], rs956868 [ 98 ], and rs12828016 [ 98 , 99 ] of the WNK1 gene ( Figure 2 C and Supplementary Table S3); and p.Ala589Ser [ 100 ] of the WNK4 gene.…”