Non-coding Single Nucleotide Variants of Renin and the (Pro)renin Receptor are Associated with Polygenic Diseases in a Bangladeshi Population.

Non-coding variants or single-nucleotide polymorphisms (SNPs) play pivotal roles in orchestrating pathogeneses of polygenic diseases, including hypertension (HTN) and diabetes. Renin-angiotensin system (RAS) components-renin and (pro)renin receptor [(P)RR]-maintain homeostasis of body fluids. Genetic variants of RAS components are associated with risk of HTN and type 2 diabetes (T2D) in different ethnic groups. We identified associations of SNPs within the renin and (P)RR genes with HTN, T2D, and T2D-associated hypertension in 911 unrelated Bangladeshi individuals. Five non-coding SNPs were involved in modulating regulatory elements in diverse cell types when tagged with other SNPs. rs61827960 was not associated with any disease; rs3730102 was associated with increased risk of HTN and T2D while under dominant model, it showed protective role against T2D-associated HTN. SNP rs11571079 was associated with increased risk of HTN and T2D-associated HTN and decreased risk of T2D, exerting a protective effect. Renin haplotypes GCA and GTG were related to increased risk of T2D and T2D-associated HTN, respectively. Heterogeneous linkage of genotypic and allelic frequencies of rs2968915 and rs3112298 of (P)RR was observed. The (P)RR haplotype GA was associated with increased risk of HTN and significantly decreased risk of T2D. These findings highlight important roles of non-coding variants of renin and (P)RR genes in the etiology of several polygenic diseases.