Ding Xiang, Hao Qiukui, Yang Ming, Chen Tie, Chen Shanping, Yue Jirong, Leng Sean X, Dong Birong
Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, NO. 37, Guoxuexiang, Chengdu, Sichuan, 610041, China.
Institute of Molecular Medicine, Health Science Center, Shenzhen University, Shenzhen, 518060, China.
BMC Med Genet. 2017 Aug 14;18(1):84. doi: 10.1186/s12881-017-0446-z.
Recent evidence indicates that ataxia telangiectasia mutated (ATM) is a cytoplasmic protein that involves in insulin signaling pathways. When ATM gene is mutated, this event appears to contribute to the development of insulin resistance and type 2 diabetes mellitus (T2DM). Up to date, little information about the relationship between ATM gene polymorphism and T2DM is available. This study aimed to explore potential association between a genetic variant [single nucleotide polymorphism (SNP), i.e. rs189037C > T] in the ATM promoter region and T2DM in older adults in China.
We conducted a 1:1 age- and sex-matched case-control study. It enrolled 160 patients including 80 type 2 diabetic and 80 nondiabetic patients who were aged 60 years and above. Genotyping of the polymorphism rs189037 in the promoter of the ATM gene was performed using polymerase chain reaction-restriction fragment length polymorphism. Chi-square test or Fisher's exact test (when an expected cell count was <5) and unpaired Student's t test were used for categorical and continuous variables, respectively. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) with adjustment for factors associated with T2DM.
Significant association was found between the genotypes of the ATM rs189037 polymorphism and T2DM (P = 0.037). The frequency of CT genotype is much higher in patients without T2DM than in diabetics (60.0% versus 40.0%, P = 0.012). After adjustment of the major confounding factors, such difference remained significant (OR for non-T2DM is 2.62, 95%CI = 1.05-6.53, P = 0.038). Similar effect of CT genotype on T2DM was observed in male population (adjusted: OR = 0.27, 95%CI = 0.09-0.84, P = 0.024). In addition, the percentage of TT genotype in diabetics with coronary artery disease (CAD) was considerably lower than in those without CAD (17.9% versus 61.5%, P = 0.004).
Our study suggests that the ATM rs189037 polymorphism is associated with reduced risk of T2DM in older adult population in China. Specifically, CT heterozygote seems to be associated with a lower risk of T2DM than CC or TT genotype, especially in male older adults. Moreover, TT genotype may reduce the risk of CAD in diabetic patients.
最近的证据表明，共济失调毛细血管扩张症突变基因（ATM）是一种参与胰岛素信号通路的胞质蛋白。当ATM基因发生突变时，这一事件似乎会促使胰岛素抵抗和2型糖尿病（T2DM）的发展。迄今为止，关于ATM基因多态性与T2DM之间关系的信息很少。本研究旨在探讨中国老年人群中ATM启动子区域的一个基因变异[单核苷酸多态性（SNP），即rs189037C>T]与T2DM之间的潜在关联。
我们进行了一项1:1年龄和性别匹配的病例对照研究。研究纳入了160例年龄在60岁及以上的患者，其中包括80例2型糖尿病患者和80例非糖尿病患者。使用聚合酶链反应-限制性片段长度多态性方法对ATM基因启动子区的rs189037多态性进行基因分型。卡方检验或Fisher精确检验（当预期单元格计数<5时）以及未配对的学生t检验分别用于分类变量和连续变量。采用逻辑回归估计比值比（OR）和95%置信区间（CI），并对与T2DM相关的因素进行校正。
发现ATM rs189037多态性的基因型与T2DM之间存在显著关联（P = 0.037）。非T2DM患者中CT基因型的频率远高于糖尿病患者（60.0%对40.0%，P = 0.012）。在调整了主要混杂因素后，这种差异仍然显著（非T2DM的OR为2.62，95%CI = 1.05 - 6.53，P = 0.038）。在男性人群中观察到CT基因型对T2DM有类似的影响（校正后：OR = 0.27，95%CI = 0.09 - 0.84，P = 0.024）。此外，患有冠状动脉疾病（CAD）的糖尿病患者中TT基因型的百分比明显低于无CAD的患者（17.9%对61.5%，P = 0.004）。
我们的研究表明，ATM rs189037多态性与中国老年人群中T2DM风险降低有关。具体而言，CT杂合子似乎比CC或TT基因型患T2DM的风险更低，尤其是在老年男性中。此外，TT基因型可能会降低糖尿病患者患CAD的风险。
