Department of Epidemiology and Health Statistics, School of Public Health, Wannan Medical College, Wuhu, 241002, Anhui, China.
Department of Hospital Infection Management Office, Wuhu Hospital of Traditional Chinese Medicine, Wuhu, 241000, Anhui, China.
Acta Diabetol. 2024 Jan;61(1):43-52. doi: 10.1007/s00592-023-02175-z. Epub 2023 Sep 5.
Type 2 diabetes mellitus (T2DM) and hypertension are common high-incidence diseases, closely related, and have common pathogenic basis such as oxidative stress. Casein kinase 2 interacting protein-1 (CKIP-1) and low-density lipoprotein receptor (LOX-1) are considered to be important factors affect the level of oxidative stress in the body. The main purpose of this study was to explore the relationship between CKIP-1 (rs6693817 A > T, rs2306235 C > G) and LOX-1 (rs1050283 G > A, rs11053646 C > G) polymorphisms and the risk of hypertension and diabetes, and try to find new candidate genes for diabetes and diabetes with hypertension etiology in Chinese population.
574 T2DM patients and 597 controls frequently matched by age and sex were selected for genotyping of CKIP-1 (rs6693817 A > T, rs2306235 C > G) and LOX-1 gene (rs1050283 G > A, rs11053646 C > G). Logistic regression was used to analyze the correlation between different genotypes and the risk of T2DM and T2DM with hypertension, and the results were expressed as odds ratio (OR) and 95% confidence interval (95% CI).
We found that the risk of T2DM in the AA + AT genotype of rs6693817 was higher than that in the TT genotype in Chinese population (OR = 1.318, 95%CI: 1.011-1.717, P = 0.041), and the difference was still significant after adjustment (OR = 1.370, 95%CI: 1.043-1.799, P = 0.024), the difference of heterozygotes (AT vs TT: OR = 1.374, 95%CI: 1.026-1.840, P = 0.033) was statistically significant. But after Bonferroni correction, the significance of the above sites disappeared. And rs6693817 was associated with the risk of T2DM combined with hypertension before and after adjustment in dominant model (OR = 1.424, 95% CI: 1.038-1.954, P = 0.028; OR = 1.460, 95% CI: 1.057-2.015, P = 0.021, respectively) and in heterozygote model (OR = 1.499, 95% CI: 1.069-2.102, P = 0.019; OR = 1.562, 95% CI: 1.106-2.207, P = 0.011, respectively). However, only the statistical significance of the heterozygous model remained after Bonferroni correction. rs2306235, rs1050283 and rs11053646 were not significantly correlated with T2DM and T2DM combined with hypertension risk (P > 0.05).
The results suggest that CKIP-1 rs6693817 is related to the susceptibility of Chinese people to T2DM with hypertension, providing a new genetic target for the treatment of diabetes with hypertension with in the future.
2 型糖尿病（T2DM）和高血压是常见的高发疾病，两者密切相关，且具有氧化应激等共同的发病基础。酪蛋白激酶 2 相互作用蛋白 1（CKIP-1）和低密度脂蛋白受体（LOX-1）被认为是影响体内氧化应激水平的重要因素。本研究的主要目的是探讨 CKIP-1（rs6693817 A > T，rs2306235 C > G）和 LOX-1（rs1050283 G > A，rs11053646 C > G）多态性与高血压和糖尿病风险之间的关系，并试图在中国人群中找到糖尿病和糖尿病伴高血压病因的新候选基因。
选择 574 例 T2DM 患者和 597 例年龄和性别相匹配的对照组进行 CKIP-1（rs6693817 A > T，rs2306235 C > G）和 LOX-1 基因（rs1050283 G > A，rs11053646 C > G）的基因分型。采用 logistic 回归分析不同基因型与 T2DM 和 T2DM 伴高血压风险的相关性，结果用比值比（OR）和 95%置信区间（95%CI）表示。
我们发现，在中国人群中，rs6693817 的 AA + AT 基因型发生 T2DM 的风险高于 TT 基因型（OR = 1.318，95%CI：1.011-1.717，P = 0.041），调整后差异仍有统计学意义（OR = 1.370，95%CI：1.043-1.799，P = 0.024），杂合子（AT 与 TT：OR = 1.374，95%CI：1.026-1.840，P = 0.033）的差异具有统计学意义。但经 Bonferroni 校正后，上述位点的显著性消失。并且，rs6693817 在显性模型（OR = 1.424，95%CI：1.038-1.954，P = 0.028；OR = 1.460，95%CI：1.057-2.015，P = 0.021）和杂合子模型（OR = 1.499，95%CI：1.069-2.102，P = 0.019；OR = 1.562，95%CI：1.106-2.207，P = 0.011）中与 T2DM 合并高血压的风险相关，且在调整后差异有统计学意义。然而，只有在 Bonferroni 校正后，杂合子模型的统计学意义仍然存在。rs2306235、rs1050283 和 rs11053646 与 T2DM 和 T2DM 合并高血压风险无显著相关性（P > 0.05）。
结果表明，CKIP-1 rs6693817 与中国人群发生 T2DM 伴高血压的易感性有关，为今后治疗高血压伴糖尿病提供了新的遗传靶点。
