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TCF7L2 基因的遗传变异及其与先前诊断为妊娠期糖尿病的立陶宛(考纳斯地区)女性人群与普通人群代谢参数的相关性。

Genetic variants of TCF7L2 gene and its coherence with metabolic parameters in Lithuanian (Kaunas district) women population with previously diagnosed gestational diabetes mellitus compared to general population.

机构信息

Institute of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.

出版信息

Diabetes Res Clin Pract. 2021 Feb;172:108636. doi: 10.1016/j.diabres.2020.108636. Epub 2020 Dec 23.

DOI:10.1016/j.diabres.2020.108636
PMID:33352264
Abstract

OBJECTIVE

To determine the association of genetic variants rs7901695, rs7903146, rs7895340, rs11196205, rs12255372 of transcription factor 7 like 2 (TCF7L2) gene and its coherence with metabolic parameters in Lithuanian (Kaunas district) women population with previously diagnosed gestational diabetes mellitus (GDM) and to compare the prevalence of TCF7L2 single nucleotide polymorphism (SNP) results to general population.

METHODS

Women with previously diagnosed GDM participated in the study. Anthropometric measurements were taken. Carbohydrate and fat metabolism were evaluated. TCF7L2 SNP common variants (rs7901695, rs7903146, rs7895340, rs11196205, rs12255372) were set. The prevalence of TCF7L2 the same SNP alleles were also evaluated for women of the general population. The results were compared to the main study group (women with previously diagnosed GDM). The results were calculated in a ratio of 1:2. General population group comprised 300 women who were selected from the random sample of the Kaunas city population. Statistical analysis was made with the statistical package IBM SPSS Statistics version 21. Quantitative parametric variables presented as mean and standard deviation, qualitative variables - as absolute numbers and percentage. ANOVA test was used, for the comparison between three or more groups. Quantitative variables were compared using Student's t-test. Categorical variables were compared using chi-square test. Correlation analysis of parametrical data was performed by Pearson's correlation. Odds ratios (OR) with 95% CIs were presented. The results were considered statistically significant at p < 0.05.

RESULTS

158 women with previously (15-47 years ago) diagnosed GDM participated in the study. The mean age of participants was 53.0 ± 8.2 years and 60.2 ± 7.5 years (p < 0.001), BMI - 31.4 ± 7.9 kg/m and 29.9 ± 5.8 kg/m (p < 0.001) in GDM group and general population respectively. GDM group women had significantly larger waist, hip circumference and waist to hip ratio compared to general population women: 98.9 ± 18.1 cm vs. 89.2 ± 13.3 (p < 0.001), 112.5 ± 14.8 cm vs. 105.6 ± 10.9 cm (p < 0.001), 0.87 ± 0.08 vs. 0.84 ± 0.07 (p < 0.001). There was no significant difference in blood pressure results between groups (p > 0.05). Carbohydrate dysmetabolism was set for 57.6% women with previously diagnosed GDM: 11 (7.0%) were diagnosed with impaired fasting glycemia (IFG), 14 (8.9%) with impaired glucose tolerance (IGT), type 2 Diabetes Mellitus (DM) was diagnosed for 58 (36.7%), DM type 1 for 7 (4.4%), MODY2 (maturity onset diabetes of the young) - 1 (0.6%) patients. TCF7L2 SNPs in women with previously diagnosed GDM and various carbohydrate metabolism groups did not differed (p > 0.05). Body weight, body mass index (BMI), waist and hip circumference in GDM group participants with different TCF7L2 SNP alleles did not differ (p > 0.05). There was no statistically significant difference in fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) results, cholesterol levels and different TCF7L2 SNP alleles in GDM group (p > 0.05). We found higher prevalence of TCF7L2 SNP rs7901695 CC/CT, rs7903146 CT/TT and rs12255372 GT/TT alleles in women previously diagnosed GDM compared to general population women's group. The OR of being in GDM group with TCF7L2 SNP: rs7901695 CC/CT alleles, was 1.703 (95% CI 1.153-2.515); rs7903146 CT/TT - 1.708 (95% CI 1.149-2.538); rs12255372 GT/TT - 1.575 (95% CI 1.058-2.343).

CONCLUSIONS

No statistically significant difference in glucose, cholesterol levels and different TCF7L2 SNP alleles in GDM group was found. TCF7L2 SNPs did not differed in women with previously diagnosed GDM and various carbohydrate metabolism groups, though a significantly higher incidence of TCF7L2 rs7901695 SNP CC/CT, rs7903146 SNP CT/TT, rs12255372 GT/TT alleles in study subjects compared to the general population women were observed.

摘要

目的

确定转录因子 7 样 2(TCF7L2)基因的 rs7901695、rs7903146、rs7895340、rs11196205、rs12255372 基因变异与立陶宛(考纳斯地区)先前诊断为妊娠糖尿病(GDM)的女性人群中的代谢参数之间的关联,并将 TCF7L2 单核苷酸多态性(SNP)结果的流行率与一般人群进行比较。

方法

患有先前诊断的 GDM 的女性参加了这项研究。测量了人体测量学指标。评估了碳水化合物和脂肪代谢。设置了 TCF7L2 SNP 常见变体(rs7901695、rs7903146、rs7895340、rs11196205、rs12255372)。还评估了一般人群中先前诊断为 GDM 的女性中 TCF7L2 相同 SNP 等位基因的流行率。将结果与主要研究组(先前诊断为 GDM 的女性)进行比较。结果按 1:2 的比例计算。一般人群组包括 300 名从考纳斯市人群中随机抽样的女性。使用 IBM SPSS Statistics 版本 21 统计包进行统计分析。定量参数变量表示为均值和标准差,定性变量表示为绝对数和百分比。使用 ANOVA 检验比较三组或更多组之间的差异。使用学生 t 检验比较定量变量。使用卡方检验比较分类变量。对参数数据进行 Pearson 相关性分析。呈现具有 95%CI 的优势比(OR)。p<0.05 时认为结果具有统计学意义。

结果

158 名先前(15-47 年前)诊断为 GDM 的女性参加了这项研究。参与者的平均年龄为 53.0±8.2 岁和 60.2±7.5 岁(p<0.001),BMI 为 31.4±7.9kg/m 和 29.9±5.8kg/m(p<0.001)在 GDM 组和一般人群中分别。与一般人群女性相比,GDM 组女性的腰围、臀围和腰臀比明显更大:98.9±18.1cm 与 89.2±13.3cm(p<0.001)、112.5±14.8cm 与 105.6±10.9cm(p<0.001)、0.87±0.08 与 0.84±0.07(p<0.001)。两组间血压结果无显著差异(p>0.05)。为 57.6%先前诊断为 GDM 的女性设置了碳水化合物代谢紊乱:11 名(7.0%)被诊断为空腹血糖受损(IFG),14 名(8.9%)被诊断为葡萄糖耐量受损(IGT),2 型糖尿病(DM)被诊断为 58 名(36.7%),1 型 DM 为 7 名(4.4%),MODY2(青年发病的成年型糖尿病)为 1 名(0.6%)患者。先前诊断为 GDM 及不同碳水化合物代谢组的女性中 TCF7L2 SNP 无差异(p>0.05)。GDM 组参与者的体重、体重指数(BMI)、腰围和臀围在不同 TCF7L2 SNP 等位基因中无差异(p>0.05)。GDM 组的空腹血糖(FPG)、口服葡萄糖耐量试验(OGTT)结果、胆固醇水平和不同 TCF7L2 SNP 等位基因无统计学差异(p>0.05)。与一般人群女性相比,我们发现先前诊断为 GDM 的女性中 TCF7L2 SNP rs7901695 CC/CT、rs7903146 CT/TT 和 rs12255372 GT/TT 等位基因的患病率更高。与 TCF7L2 SNP 相比,GDM 组的优势比(OR)为 rs7901695 CC/CT 等位基因 1.703(95%CI 1.153-2.515);rs7903146 CT/TT-1.708(95%CI 1.149-2.538);rs12255372 GT/TT-1.575(95%CI 1.058-2.343)。

结论

GDM 组的血糖、胆固醇水平和不同的 TCF7L2 SNP 等位基因无统计学差异。先前诊断为 GDM 的女性与不同碳水化合物代谢组的 TCF7L2 SNP 无差异,但与一般人群女性相比,研究对象中 TCF7L2 rs7901695 SNP CC/CT、rs7903146 SNP CT/TT、rs12255372 GT/TT 等位基因的发生率明显更高。

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