Association between plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipids with rs7903146 polymorphisms of the TCF7L2 gene in diabetic patients

The rs7903146 polymorphism of TCF7L2 gene is known as the strongest genetic risk factor for type 2 diabetes mellitus (T2DM). The polymorphism is in association with clinical profile of T2DM patients. PCSK9 is a serine protease that promotes LDLR degradation and regulates circulating levels of lipids. The association of this polymorphism with PCSK9 and metabolic profile of diabetic and healthy subjects was investigated. This cross-sectional study was performed on 132 T2DM patients and the same number of healthy subjects. All the participants were genotyped for the rs7903146 single nucleotide polymorphism by the PCR-RFLP method. Metabolic profile including plasma levels of PCSK9, triglycerides, total cholesterol, non-HDL cholesterol, LDL cholesterol, HDL cholesterol, fasting plasma glucose, and HBA1C was measured. PCSK9, total cholesterol, and LDL-C levels were lower in the diabetic patients as compared to the healthy subjects. There were also direct and significant associations between PCSK9 and TG, TC, LDL-C, and non HDL-C in the subjects. Values of plasma glucose, HbA1c, PCSK9, TC, and LDL-C were higher in patients with TT genotype, but the differences were not statistically significant for all. A positive Spearman correlation was found between PCSK9 levels and the genotypes in all the participants. The results confirm the association of rs7903146 in the TCF7L2 gene with metabolic parameters and PCSK9. The T allele was associated with higher lipid and PCSK9 levels.

     

Association of the rs3758391 polymorphism in the SIRT1 gene with diabetic nephropathy and decreased estimated glomerular filtration rate (GFR) in a population from southwest Iran

Introduction

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disorder. SIRT1 has an essential role in the insulin-signaling pathway and energy homeostasis. SIRT1 exerts protective effects in the kidney cells.

Objectives

We aimed to investigate whether the rs3758391 variant was associated with diabetic nephropathy, measures of kidney function, and BMI in a population with and without diabetes in southwest Iran.

Methods

The study comprised 132 patients with type 2 diabetes mellitus (T2DM) (with and without nephropathy). They were compared with 66 normal subjects. The subjects were genotyped for the rs3758391 polymorphism by the PCR–RFLP method. Fasting blood glucose, HbA1c, urea, creatinine, and urinary albumin were measured using a biochemistry analyzer. Serum cystatin C levels were measured by ELISA.

Results

The genotype distribution and allele frequencies were significantly different between the entirely diabetic group and the healthy subjects (p value < 0.05). For T2DM, the odds ratios (ORs) for the TT genotype and the T allele carrier were 5.7 (95% confidence interval (CI) 2.2–14.9, p < 0.001) and 4.01 (95% CI 2.1–7.5, p < 0.001), respectively. For diabetic nephropathy, the ORs for the TT genotype and the T allele carrier were 3.96 (95% CI 1.5–10.0, p = 0.003) and 3.0 (95% CI 1.4–6.4, p = 0.003), respectively. For decreased eGFR below 60 mL/min/1.73m², the OR for TT was 2.9 (95% CI 1.1–7.5, p = 0.02).

Conclusion

Our results confirm that the risk allele of the rs3758391 SNP in the SIRT1 gene is strongly associated with T2DM and diabetic nephropathy. The TT genotype is also associated with decreased eGFR.