Associations between INSR and MTOR polymorphisms in type 2 diabetes mellitus and diabetic nephropathy in a Northeast Chinese Han population

Abstract

ABSTRACT. We explored the associations of INSR and mTOR, 2 key genes in the insulin signaling pathway, and the susceptibility to type 2 diabetes mellitus and diabetic nephropathy. Three single-nucleotide polymorphisms (SNPs) (rs1799817, rs1051690, and rs2059806) in INSR and 3 SNPs (rs7211818, rs7212142, and rs9674559) in mTOR were genotyped using the Sequenom MassARRAY iPLEX platform in 89 type 2 diabetes patients without diabetic nephropathy, 134 type 2 diabetes patients with diabetic nephropathy, and 120 healthy control subjects. Statistical analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Combination analyses between rs2059806 and rs7212142 were also performed using the c 2 test and logistic regression. Among these 6 SNPs, 4 (rs1799817, rs1051690, rs7211818, and rs9674559) showed no INSR and MTOR associated with T2DM and type 2 DN association with type 2 diabetes mellitus or diabetic nephropathy. However, rs2059806 in INSR was associated with both type 2 diabetes mellitus (P = 0.033) and type 2 diabetic nephropathy (P = 0.018). The rs7212142 polymorphism in mTOR was associated with type 2 diabetic nephropathy (P = 0.010, OR = 0.501, 95%CI = 0.288-0.871), but showed no relationship with type 2 diabetes mellitus. Combination analysis revealed that rs2059806 and rs7212142 had a combined effect on susceptibility to type 2 diabetes mellitus and diabetic nephropathy. Our results suggest that both INSR and mTOR play a role in the predisposition of the Han Chinese population to type 2 diabetic nephropathy, but the genetic predisposition may show some differences.

The genetic susceptibility profile of type 2 diabetes and reflection of its possible role related to reproductive dysfunctions in the southern Indian population of Hyderabad

“…Further, INSR is involved in adipogenesis and beta-cell insulin secretion and mutations in this gene leads to T2DM [ 64 ]. Concurrently, the rs2059806 of INSR gene which is located in the coding region of exon 8 and known to cause synonymous change was found to be associated with risk for T2DM in the present study and in Han-Chinese [ 65 ]. Whereas another SNP of INSR, rs1799817-A, showed protective nature of association towards T2DM in our study and in another sample of south Indians from Chennai [ 66 ], it was not associated in Han-Chinese population [ 65 ].…”

Metastatic colorectal cancer and type 2 diabetes: prognostic and genetic interactions

“…Most important, their cumulative effect is unpredictable and we cannot rule out the hypothesis that a “critical” cumulative, although benign, effect could contribute and prompt the malignancy. Interestingly, the genomic landscape of unselected metastatic CRC patients is rich in somatically mutated genes involved in T2D, as evidenced in previously published studies [42–49]. The effects of these variants are unexplored, elusive, largely invaluable in functional and clinical point of views.…”

Sestrin2 Signaling Pathway Regulates Podocyte Biology and Protects against Diabetic Nephropathy

“…Diabetic nephropathy is characterized by mTORC1 overactivity in the kidney biopsies from diabetic patients and diabetic mice [135,136]. Interestingly, the rs7212142 polymorphism in mTORC1 gene has been significantly associated with diabetic nephropathy in the Chinese population [137]. The basal and physiologic function of mTORC1 is critical for the normal function of the kidney as it was shown that podocyte-specific deletion of mTORC1 leads to decreased adaptation to stress conditions and more severe glomerulosclerosis in diabetic mice [135].…”