Non-coding Single Nucleotide Variants of Renin and the (Pro)renin Receptor are Associated with Polygenic Diseases in a Bangladeshi Population
Non-coding Single Nucleotide Variants of Renin and the (Pro)renin Receptor are Associated with Polygenic Diseases in a Bangladeshi Population
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DOI：
10.1007/s10528-021-10049-8
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发表时间：
2021-03
影响因子：
2.4
通讯作者：
Jobaida Akther;A. Das;M. A. Rahman;S. Saha;Md. Ismail Hosen;A. Ebihara;T. Nakagawa;F. Suzuki;A. Nabi
中科院分区：
文献类型：
--
作者：
Jobaida Akther;A. Das;M. A. Rahman;S. Saha;Md. Ismail Hosen;A. Ebihara;T. Nakagawa;F. Suzuki;A. Nabi
非编码变异或单核苷酸多态性（SNPs）在多基因疾病（包括高血压（HTN）和糖尿病）的发病机制中起着关键作用。肾素-血管紧张素系统（RAS）组分--肾素和（原）肾素受体[（P）RR]--维持体液的稳态。RAS组分的遗传变异与不同种族人群中HTN和2型糖尿病（T2 D）的风险相关。我们在911名无关的孟加拉人中确定了肾素和（P）RR基因内的SNP与HTN、T2 D和T2 D相关高血压的相关性。五个非编码SNPs参与调制调节元件在不同的细胞类型时，与其他SNPs标记。rs61827960与任何疾病无关; rs3730102与HTN和T2 D的风险增加相关，而在显性模型下，它对T2 D相关的HTN显示出保护作用。SNP rs 11571079与HTN和T2 D相关HTN的风险增加以及T2 D风险降低相关，具有保护作用。肾素单倍型GCA和GTG分别与T2 D和T2 D相关HTN的风险增加相关。（P）RR的rs 2968915和rs3112298位点的基因型和等位基因频率存在异质性连锁。（P）RR单倍型GA与HTN风险增加和T2 D风险显著降低相关。这些发现突出了肾素和（P）RR基因的非编码变体在几种多基因疾病的病因学中的重要作用。
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.