Genetic variants in PTPRD and risk of gestational diabetes mellitus.
Genetic variants in PTPRD and risk of gestational diabetes mellitus.
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PTPRD 的遗传变异与妊娠期糖尿病的风险
DOI：
10.18632/oncotarget.12599
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发表时间：
2016-11-15
期刊：
影响因子：
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通讯作者：
Wang X
中科院分区：
文献类型：
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作者：
Chen T;Xu J;Liu G;Liu H;Chen M;Qin Y;Wu W;Xia Y;Ji C;Guo X;Wen J;Wang X
全基因组关联研究 (GWAS) 显示 D 型蛋白酪氨酸磷酸酶受体 (PTPRD) 中的两个单核苷酸多态性 (SNP)（rs17584499 和 rs649891）与 2 型糖尿病 (T2D) 相关。我们试图确定 PTPRD 变异对妊娠糖尿病 (GDM) 风险的影响。在这项研究中，使用 Sequenom 平台对 T2D GWAS 中报告的 PTPRD 中的两个 SNP 和 964 个 GDM 病例和 1,021 个对照中的 6 个 PTPRD 表达相关 SNP 进行了基因分型。加法模型中的逻辑回归分析显示，PTPRD rs10511544 A>C、rs10756026 T>A 和 rs10809070 C>G 与 GDM 风险降低始终显着相关[调整后 OR (95% CI) = 0.83 (0.72-0.97)，rs10511544； rs10756026 的调整 OR (95% CI) = 0.81 (0.70-0.94)； rs10809070 的调整 OR (95% CI) = 0.78 (0.65-0.92)]。此外，随着三个 SNP 的变异等位基因数量的增加，GDM 的风险显着降低，且呈剂量依赖性 (Ptrend = 0.008)。此外，与最常见的单倍型相比，包含三个 SNP 变异等位基因的单倍型与 GDM 风险降低显着相关 [调整后 OR (95% CI) = 0.77 (0.64-0.92)，P = 0.005]。然而，T2D GWAS 中报告的 SNP 没有显着关联。总之，这些发现表明 PTPRD 中 rs10511544、rs10756026 和 rs10809070 的变异可能有助于降低 GDM 的易感性。需要在不同种族背景和生物学功能分析中进一步验证。
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.