Frontiers in cell and developmental biology · 2026
CDKN2A/2B gene variants and gene-environment interactions increase the risk of gestational diabetes mellitus in Chinese women.
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Zhang Yi, Yang Runqiu, Wang Xin, Yu Hongsong
Аннотация
INTRODUCTION: This study investigates the association between the cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) gene and gestational diabetes mellitus (GDM) in Chinese women, with a focus on potential gene-environment interactions.
METHODS: A case-control study was conducted with 1,566 pregnant women from Beijing, Wuhan, and Zunyi, China. Blood samples were analyzed using targeted next-generation sequencing. Logistic regression was applied to examine the relationship between gene polymorphisms, environmental exposures, and GDM. Gene-environment interactions were assessed using Excel tools developed by Knol and Andersson et al.
RESULTS: Genetic analysis revealed significant associations between two of the three loci: rs23832080 (P = 0.002, OR = 0.801) and rs10811661 (P = 0.00055, OR = 0.746), and GDM. Haplotype analysis showed that haplotypes of these loci were correlated with GDM (AGC: P = 0.002, OR = 0.784; AAT: P = 0.024, OR = 1.183; GAT: P = 0.043, OR = 1.247). Environmental exposure analysis indicated that ozone (O3) and PM2.5 were associated with GDM. Interaction analysis revealed that the wild-type alleles of rs2383208 and rs10811661 interacted with O3, increasing the risk of GDM, while the wild-type allele of rs10811661 also interacted with PM2.5, further elevating GDM risk.
CONCLUSION: CDKN2A/2B gene polymorphisms, haplotypes, environmental exposure to O3 and PM2.5, and gene-environment interactions contribute to an increased risk of GDM in Chinese women.
TRIAL REGISTRATION: Chinese Clinical Trial Registry, chictr.org.cn, ChiCTR2000029178.
METHODS: A case-control study was conducted with 1,566 pregnant women from Beijing, Wuhan, and Zunyi, China. Blood samples were analyzed using targeted next-generation sequencing. Logistic regression was applied to examine the relationship between gene polymorphisms, environmental exposures, and GDM. Gene-environment interactions were assessed using Excel tools developed by Knol and Andersson et al.
RESULTS: Genetic analysis revealed significant associations between two of the three loci: rs23832080 (P = 0.002, OR = 0.801) and rs10811661 (P = 0.00055, OR = 0.746), and GDM. Haplotype analysis showed that haplotypes of these loci were correlated with GDM (AGC: P = 0.002, OR = 0.784; AAT: P = 0.024, OR = 1.183; GAT: P = 0.043, OR = 1.247). Environmental exposure analysis indicated that ozone (O3) and PM2.5 were associated with GDM. Interaction analysis revealed that the wild-type alleles of rs2383208 and rs10811661 interacted with O3, increasing the risk of GDM, while the wild-type allele of rs10811661 also interacted with PM2.5, further elevating GDM risk.
CONCLUSION: CDKN2A/2B gene polymorphisms, haplotypes, environmental exposure to O3 and PM2.5, and gene-environment interactions contribute to an increased risk of GDM in Chinese women.
TRIAL REGISTRATION: Chinese Clinical Trial Registry, chictr.org.cn, ChiCTR2000029178.