# Association between KCNQ1 gene polymorphisms and gestational diabetes mellitus susceptibility in a Chinese population

**Authors:** Yanying Wu, Yuxuan Zhang, Xin Liu, Jia Liu, Zhaotao He, Yue Wei, Qiaoli Zeng, Runmin Guo

PMC · DOI: 10.3389/fendo.2025.1451942 · Frontiers in Endocrinology · 2025-07-02

## TL;DR

This study finds that a specific genetic variant in the KCNQ1 gene is linked to a lower risk of gestational diabetes in a Chinese population.

## Contribution

The study identifies a novel association between KCNQ1 gene polymorphism rs2237897 and reduced gestational diabetes risk in young Chinese women.

## Key findings

- rs2237897 is associated with decreased gestational diabetes risk in women under 30 years old.
- Meta-analysis confirms rs2237892 is linked to reduced gestational diabetes risk across different populations.
- rs151290 and rs163184 showed no significant association with gestational diabetes in the studied population.

## Abstract

The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene is recognized as a type 2 diabetes mellitus (T2DM) susceptibility gene. However, there is limited data regarding the association between KCNQ1 gene polymorphisms and gestational diabetes mellitus (GDM) susceptibility in China. To explore the association between KCNQ1 gene polymorphisms and GDM susceptibility in a Chinese population.

We conducted a case-control study including 500 pregnant women with GDM and 502 pregnant women with normal glucose tolerance (as controls). Blood samples and clinical data were collected. KCNQ1 gene rs2237897, rs163184, rs151290, and rs2237892 were genotyped by SNPscan™ genotyping assay. Using SPSS V.26.0, statistical analysis was performed to explore the association of KCNQ1 gene polymorphisms with GDM and genotypes with blood glucose levels. Meta-analysis was further validated in different populations.

After being adjusted for confounding factors (age, parity, pre-pregnancy BMI (pre-BMI) and blood pressure) and Bonferroni correction, rs2237897 showed an association with decreased GDM risk in codominant heterozygous (CT vs. CC: OR = 0.537; 95% CI: 0.354-0.816; P = 0.004) and overdominant models (CT vs. CC+TT: OR = 0.533; 95% CI: 0.355-0.801; P = 0.002) in pregnant women aged < 30 years. However, rs2237892, rs151290, and rs163184 did not found associations with GDM after Bonferroni correction. Meta-analysis showed that rs2237892 was associated with decreased GDM risk in different races in dominant (TC+TT vs. CC: OR = 0.830; 95% CI: 0.699-0.985; P = 0.033), recessive (TT vs. CT+CC: OR = 0.733; 95% CI: 0.612-0.877; P = 0.001), codominant homozygous (TT vs. CC: OR = 0.679; 95% CI: 0.562-0.820; P < 0.001), codominant heterozygous (TC vs. CC: OR = 0.843; 95% CI: 0.753-0.945; P = 0.003) and allele models (T vs. C: OR = 0.852; 95% CI: 0.740-0.982; P = 0.027).

KCNQ1 rs2237897 is associated with decreased GDM risk in a Chinese population. Although rs2237892 did not found association with GDM risk in our subjects, meta-analysis confirmed that rs2237892 is associated with reduced GDM risk across different populations. Further studies are needed to confirm these findings and elucidate the mechanisms.

## Linked entities

- **Genes:** KCNQ1 (potassium voltage-gated channel subfamily Q member 1) [NCBI Gene 3784]
- **Diseases:** gestational diabetes mellitus (MONDO:0005406), type 2 diabetes mellitus (MONDO:0005148)

## Full-text entities

- **Genes:** KCNQ1 (potassium voltage-gated channel subfamily Q member 1) [NCBI Gene 3784] {aka ATFB1, ATFB3, JLNS1, KCNA8, KCNA9, KVLQT1}
- **Diseases:** T2DM (MESH:D003924), GDM (MESH:D016640)
- **Chemicals:** blood glucose (MESH:D001786)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs2237892, rs2237897, rs151290, rs163184

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12263388/full.md

## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12263388/full.md

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Source: https://tomesphere.com/paper/PMC12263388