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

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: gestational diabetes mellitus; potassium voltage-gated channel subfamily Q member 1; rs151290; rs163184; rs2237892; rs2237897; single nucleotide polymorphism.

Figure 1

Flow chart of the literature search and selection.

Figure 2

Linkage disequilibrium (LD) between multiple loci of the KCNQ1 gene (rs163184, rs151290 and rs2237892). (A) coefficient of linkage disequilibrium D’; (B) correlation coefficient R².

Figure 3

Meta-analysis of the association between KCNQ1 rs2237892 and GDM susceptibility. (A) dominant model, TT+CT vs. CC; (B) recessive model, TT vs. CT+CC; (C) overdominant model, CT vs. TT+CC; (D) codominant homozygous model, TT vs. CC; (E) codominant heterozygous model, CT vs. CC; (F) allele model, T vs. (C) OR, odds ratio; CI, confidence interval; I-squared, measure to quantify the degree of heterogeneity in meta-analyses.

Figure 4

Meta-analysis of the association between KCNQ1 rs151290 and GDM susceptibility. (A) dominant model, AA+CA vs. CC; (B) recessive model, AA vs. CA+CC; (C) overdominant model, CA vs. AA +CC; (D) codominant homozygous model, AA vs. CC; (E) codominant heterozygous model, CA vs. CC; (F) allele model, A vs. (C) OR, odds ratio; CI, confidence interval; I-squared, measure to quantify the degree of heterogeneity in meta-analyses.