AUTHOR=Zeng Qiaoli , Yang Taili , Wei Wenfeng , Zou Dehua , Wei Yue , Han Fengqiong , He Jieyun , Huang Jinzhi , Guo Runmin 

TITLE=Association between GLO1 variants and gestational diabetes mellitus susceptibility in a Chinese population: a preliminary study

JOURNAL=Frontiers in Endocrinology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1235581

DOI=10.3389/fendo.2023.1235581

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p><italic>Glyoxalase 1</italic> (<italic>GLO1</italic>) plays a crucial role in defending against glycation. Single nucleotide polymorphism (SNP) variants in the <italic>GLO1</italic> gene may affect gene expression and alter enzyme activity. However, there have been limited studies evaluating the association between <italic>GLO1</italic> and diabetes, especially gestational diabetes mellitus (GDM). Therefore, this study is the first to explore the association of <italic>GLO1</italic> SNPs and GDM risk.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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 (<italic>P</italic> &lt; 0.05). After adjusting for these factors, <italic>GLO1</italic> rs1130534 TA remained associated with an increased risk of GDM (TA <italic>vs</italic>. TT + AA: OR = 1.320; 95% CI: 1.008-1.728; <italic>P</italic> = 0.044), especially in the pre-BMI ≥ 24 subgroup (TA <italic>vs</italic>. TT + AA: OR = 2.424; 95% CI: 1.048-5.607; <italic>P</italic> = 0.039), with fasting glucose levels being significantly elevated in the TA genotype compared to the TT genotype (<italic>P</italic> &lt; 0.05). Conversely, the <italic>GLO1</italic> rs4746 TG was associated with a decreased risk of GDM (TG <italic>vs</italic>. TT: OR = 0.740; 95% CI: 0.548-0.999; <italic>P</italic> = 0.049; TG <italic>vs</italic>. TT + GG: OR = 0.740; 95% CI: 0.548-0.998; <italic>P</italic> = 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; <italic>P</italic> = 0.038). Furthermore, the rs1781735 GG genotype was found to be more closely related to maternal MG accumulation and neonatal weight gain (<italic>P</italic> &lt; 0.05).</p></sec><sec><title>Conclusion</title><p>Our findings suggested that <italic>GLO1</italic> rs1130534 was associated with an increased susceptibility to GDM and higher blood glucose levels, but <italic>GLO1</italic> 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.</p></sec>