背景:心脏自主神经病变(CAN)是糖尿病(DM)的并发症,通过破坏心脏神经支配而增加发病率和死亡率的风险。最近的证据表明,即使在DM发作之前,CAN也可能出现,糖尿病前期和代谢综合征可能是前体。这项研究旨在通过调查特定基因的SNP来确定与哈萨克族人群中CAN发育相关的遗传标记。
方法:一项病例对照研究涉及82例CAN患者(病例)和100例无CAN患者(对照)。从RSE“哈萨克斯坦共和国总统事务管理局医疗中心医院”附属医院共招募了182名哈萨克族人。FTO基因的7个SNP,PPARG,SNCA,对XRCC1、FLACC1/CASP8停止了研讨。使用卡方方法进行统计分析,用95%置信区间(CI)计算优势比(OR),和SPSS26.0中的逻辑回归。
结果:在SNCA基因多态性中,rs2737029与CAN显著相关,CAN的风险几乎翻了一番(OR2.03(1.09-3.77),p=0.03)。然而,用SNCA基因的rs2736990检测到与CAN无统计学意义的关联(OR1.00CI(0.63-1.59),p=0.99)。FTO基因的rs12149832使CAN的风险增加了三倍(OR3.22(1.04-9.95),p=0.04),而PPARG基因的rs1801282和FLACC1基因的rs13016963增加了两倍的风险(OR2.56(1.19-5.49),p=0.02)和(OR2.34(1.00-5.46),p=0.05)。XRCC1基因的rs1108775和rs1799782与调整前后发生CAN的机会减少有关(OR0.24,CI(0.09-0.68),p=0.007,OR0.43,CI(0.22-0.84),分别为p=0.02)。
结论:研究表明rs2737029(SNCA基因),rs12149832(FTO基因),rs1801282(PPARG基因),rs13016963(FLACC1基因)可能是CAN发生的诱发因素。此外,SNPsrs1108775和rs1799782(XRCC1基因)可赋予对CAN的抗性。SNCA基因只有一个rs2736990多态性与CAN无关。
BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes.
METHODS: A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE \"Medical Center Hospital of the President\'s Affairs Administration of the Republic of Kazakhstan\". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0.
RESULTS: Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively).
CONCLUSIONS: The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.