Association of genetic polymorphisms of PCSK9 with type 2 diabetes in Uygur Chinese population

Abstract

Background PCSK9 gene expression is associated with biological processes such as lipid metabolism, glucose metabolism, and inflammation. In the present study, our primary objective was to assess the association between the single-nucleotide polymorphisms in the PCSK9 gene and type 2 diabetes in Uygur subjects, in Xinjiang, China. Methods We designed a case–control study including 662 patients diagnosed with T2DM and 1220 control subjects. Four single-nucleotide polymorphisms (rs11583680, rs2483205, rs2495477 and rs562556) of PCSK9 gene were genotyped using the improved multiplex ligation detection reaction technique. Results For rs2483205, the distribution of genotypes, dominant model (CC vs CT + TT), overdominant model (CC + TT vs CT) showed significant differences between T2DM patients and the controls (P = 0.011 and P = 0.041 respectively). For rs2495477, the distribution of genotypes, the dominant model (AA vs GA + GG) showed significant differences between T2DM patients and the controls (P = 0.024). Logistic regression analysis suggested after adjustment of other confounders, the differences remained significant between the two groups [for rs2483205 CC vs CT + TT: odds ratio (OR) = 1.321, 95% confidence interval (CI) 1.078–1.617, P = 0.007; CC + TT vs CT: OR = 1.255, 95% CI 1.021–1.542, P = 0.03; for rs2495477 AA vs GA + GG: OR = 1.297, 95% CI 1.060–1.588, P = 0.012]. Conclusion The present study indicated that CT + TT genotype and CT genotype of rs2483205, as well as GA + GG genotype of rs2495477 in PCSK9 gene were associated with an increased risk of type 2 diabetes in the Uygur population in Xinjiang.

Association between serum PCSK9 and coronary heart disease in patients with type 2 diabetes mellitus

“…To the best of our knowledge, this is the first large-scale longitudinal study on the relationship between circulating PCSK9 and the prediction of clinical cardiovascular outcomes in Chinese individuals with T2DM. Previous studies reported increased plasma PCSK9 levels in patients with T2DM [ 18 , 21 , 22 ]. Moreover, among young participants, plasma PCSK9 levels are also increased in T1DM; as glycemic control deteriorates, plasma PCSK9 levels increase significantly [ 23 ].…”

“…To explore the relationship between PCSK9 and CHD severity, we divided the patients in the CHD group into four subgroups based on the quartile of PCSK9 levels (Supplementary Table 1). We observed that the percentage of patients with three-vessel disease (17.30% vs. 31.01% vs. 50.45% vs. 66.52%, p < 0.001) and GS [23 (21) vs. 30 (21) vs. 36 (24) vs. 46 (20), p < 0.001] increased in the high PCSK9 group, whereas the percentage of patients with one-vessel disease decreased (p < 0.001), indicating that PCSK9 levels may be associated with CHD severity. Furthermore, Spearman's correlation analysis showed that serum PCSK9 levels were significantly and positively associated with diseased vessels and GS (r = 0.35, p < 0.001; r = 0.46, p < 0.001, respectively) (Fig.…”

“…Most importantly, circulating PCSK9 has been recognized as an adverse cardiovascular risk factor in patients with CAD [18,19]. Owing to the close relationship between lipid and glucose metabolism, an increasing number of studies have found a close relationship between PCSK9 and diabetes [20,21]. However, the pathogenicity of PCSK9 in T2DM patients and T2DM patients with CHD has not been completely established.…”