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The present prospective study included 2156 women and investigated the effect of gene variants in the vitamin D (VitD) metabolic and glucose pathways and their interaction with VitD levels during pregnancy on gestational diabetes mellitus (GDM). Plasma 25(OH)D concentrations were measured at the first and second trimesters. GDM subtype 1 was defined as those with isolated elevated fasting plasma glucose; GDM subtype 2 were those with isolated elevated postprandial glucose at 1 h and/or 2 h; and GDM subtype 3 were those with both elevated fasting plasma glucose and postprandial glucose. Six Gc isoforms were categorized based on two GC gene variants rs4588 and rs7041, including 1s/1s, 1s/2, 1s/1f, 2/2, 1f/2 and 1f/1f. VDR-rs10783219 and MTNR1B-rs10830962 were associated with increased risks of GDM and GDM subtype 2; interactions between each other as well as with CDKAL1-rs7754840 were observed (Pinteraction &lt; 0.05). Compared with the 1f/1f isoform, the risk of GDM subtype 2 among women with 1f/2, 2/2, 1s/1f, 1s/2 and 1s/1s isoforms and with prepregnancy body mass index ≥24 kg/m2 increased by 5.11, 10.01, 10, 14.23, 19.45 times, respectively. Gene variants in VitD pathway interacts with VitD deficiency at the first trimester on the risk of GDM and GDM subtype 2.

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The Association of Gene Variants in the Vitamin D Metabolic Pathway and Its Interaction with Vitamin D on Gestational Diabetes Mellitus: A Prospective Cohort Study