Genetic variants in PTPRD and risk of gestational diabetes mellitus.

Juan Xu,Wei Wu,Juan Wen,Xirong Guo,Ting Chen,Guangquan Liu,Chenbo Ji,Minjian Chen,Heng Liu,Yankai Xia,Yufeng Qin,Xinru Wang

doi:10.18632/oncotarget.12599

Abstract

Genome-wide association studies (GWASs) showed that two single nucleotide polymorphisms (SNPs) (rs17584499 and rs649891) in the protein tyrosine phosphatase receptor type D (PTPRD) were associated with type 2 diabetes (T2D). We sought to determine the influence of the PTPRD variants on the gestational diabetes mellitus (GDM) risk. In this research, two SNPs in PTPRD reported in T2D GWASs and six PTPRD expression-related SNPs were genotyped in 964 GDM cases and 1,021 controls using the Sequenom platform. Logistic regression analyses in additive models showed consistently significant associations of PTPRD rs10511544 A>C, rs10756026 T>A and rs10809070 C>G with a decreased risk of GDM [adjusted OR (95% CI) = 0.83 (0.72-0.97) for rs10511544; adjusted OR (95% CI) = 0.81 (0.70-0.94) for rs10756026; adjusted OR (95% CI) = 0.78 (0.65-0.92) for rs10809070]. Furthermore, the risk of GDM was significantly decreased with an increasing number of variant alleles of the three SNPs in a dose-dependent manner (Ptrend = 0.008). Moreover, the haplotype containing variant alleles of the three SNPs were significantly associated with a decreased risk of GDM [adjusted OR (95% CI) = 0.77 (0.64-0.92), P = 0.005], when compared with the most frequent haplotype. However, there were no significant associations for the SNPs reported in the T2D GWASs. Altogether, these findings indicate that the variants of rs10511544, rs10756026 and rs10809070 in PTPRD may contribute to a decreased susceptibility to GDM. Further validation in different ethnic backgrounds and biological function analyses are needed.

Highlights

Gestational diabetes mellitus (GDM) is defined as varying degrees of glucose intolerance with an onset or first recognition during pregnancy [1]
Two single nucleotide polymorphisms (SNPs) in phosphatase receptor type D (PTPRD) reported in type 2 diabetes (T2D) Genome-wide association studies (GWASs) and six PTPRD expression-related SNPs were genotyped in 964 gestational diabetes mellitus (GDM) cases and 1,021 controls using the Sequenom platform
We did not validate the results of the PTPRD variations reported in the published GWASs for T2D, but we observed that PTPRD rs10511544 A>C, rs10756026 T>A and rs10809070 C>G were significantly associated with a decreased risk of GDM using the additive model [adjusted odds ratios (OR) = 0.83 (0.72-0.97) for rs10511544; adjusted OR = 0.81 (0.70-0.94) for rs10756026; adjusted OR = 0.78 (0.65-0.92) for rs10809070] (Table 2-3)

Summary

Introduction

Gestational diabetes mellitus (GDM) is defined as varying degrees of glucose intolerance with an onset or first recognition during pregnancy [1]. The incidence of GDM has steadily risen in the last few decades and affects 1%-14% of all pregnancies [2]. Both GDM patients and their children have an increased risk of developing type 2 www.impactjournals.com/oncotarget diabetes (T2D) and metabolic syndrome later in life [3]. In the past few decades, genetic studies, including genome-wide association studies (GWASs) and candidate gene strategies, have identified many susceptibility genes involved in the increased risk of T2D and GDM [6, 7]. The PTPRD genetic variant was suggested to be associated with progression to diabetes in Han Chinese, most likely through increased insulin resistance [11].

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Results

Conclusion