■乙二醛酶1(GLO1)在防御糖基化中起着至关重要的作用。GLO1基因中的单核苷酸多态性(SNP)变体可能会影响基因表达并改变酶活性。然而,有有限的研究评估GLO1和糖尿病之间的关联,尤其是妊娠期糖尿病(GDM)。因此,本研究首次探讨GLO1SNPs与GDM风险的相关性。
■该研究包括总共500名GDM患者和502名对照受试者。SNPscan™基因分型测定用于rs1781735、rs4746和rs1130534的基因分型。为了评估基因型的差异,等位基因,和单倍型分布及其与GDM风险的相关性,独立样本t检验,逻辑回归,在数据处理阶段采用卡方检验。此外,进行了单因素方差分析,以确定基因型,血糖和甲基乙二醛(MG)水平的差异.
■孕前体重指数(BMI)存在显着差异,年龄,收缩压(SBP),舒张压(DBP),GDM和健康受试者之间的均等(P<0.05)。在调整了这些因素后,GLO1rs1130534TA仍然与GDM风险增加相关(TA与TT+AA:OR=1.320;95%CI:1.008-1.728;P=0.044),特别是在前BMI≥24亚组(TA与TT+AA:OR=2.424;95%CI:1.048-5.607;P=0.039),与TT基因型相比,TA基因型的空腹血糖水平显着升高(P<0.05)。相反,GLO1rs4746TG与GDM风险降低相关(TG与TT:OR=0.740;95%CI:0.548-0.999;P=0.049;TGvs.TT+GG:OR=0.740;95%CI:0.548-0.998;P=0.048)。此外,在BMI≥24的个体中,rs1781735,rs4746和rs1130534的单倍型T-G-T与GDM风险降低相关(OR=0.423;95%CI:0.188~0.955;P=0.038).此外,发现rs1781735GG基因型与母体MG积累和新生儿体重增加更密切相关(P<0.05)。
■我们的研究结果表明,GLO1rs1130534与GDM易感性增加和血糖水平升高有关,但GLO1rs4746与GDM风险降低相关.rs1781735与母体MG的积累和随后的新生儿体重增加有关。
Glyoxalase 1 (GLO1) plays a crucial role in defending against glycation. Single nucleotide polymorphism (SNP) variants in the GLO1 gene may affect gene expression and alter enzyme activity. However, there have been limited studies evaluating the association between GLO1 and diabetes, especially gestational diabetes mellitus (GDM). Therefore, this study is the first to explore the association of GLO1 SNPs and GDM risk.
The study included a total of 500 GDM patients and 502 control subjects. The SNPscan™ genotyping assay was used to genotype rs1781735, rs4746 and rs1130534. To assess the disparities in genotype, allele, and haplotype distributions and their correlation with GDM risk, the independent sample t-test, logistic regression, and chi-square test were employed during the data processing phase. Furthermore, one-way ANOVA was conducted to determine the differences in genotype and blood glucose and methylglyoxal(MG) levels.
Significant differences were observed in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP), and parity between GDM and healthy subjects (P < 0.05). After adjusting for these factors, GLO1 rs1130534 TA remained associated with an increased risk of GDM (TA vs. TT + AA: OR = 1.320; 95% CI: 1.008-1.728; P = 0.044), especially in the pre-BMI ≥ 24 subgroup (TA vs. TT + AA: OR = 2.424; 95% CI: 1.048-5.607; P = 0.039), with fasting glucose levels being significantly elevated in the TA genotype compared to the TT genotype (P < 0.05). Conversely, the GLO1 rs4746 TG was associated with a decreased risk of GDM (TG vs. TT: OR = 0.740; 95% CI: 0.548-0.999; P = 0.049; TG vs. TT + GG: OR = 0.740; 95% CI: 0.548-0.998; P = 0.048). Additionally, the haplotype T-G-T of rs1781735, rs4746 and rs1130534 was associated with a decreased risk of GDM among individuals with a pre-BMI ≥ 24 (OR = 0.423; 95% CI: 0.188-0.955; P = 0.038). Furthermore, the rs1781735 GG genotype was found to be more closely related to maternal MG accumulation and neonatal weight gain (P < 0.05).
Our findings suggested that GLO1 rs1130534 was associated with an increased susceptibility to GDM and higher blood glucose levels, but GLO1 rs4746 was associated with a decreased risk of GDM. The rs1781735 has been associated with the accumulation of maternal MG and subsequent weight gain in neonates.