MTNR1B基因多态性作为妊娠期糖尿病的危险因素：在单一三级医疗中心进行的病例对照研究
MTNR1B genetic polymorphisms as risk factors for gestational diabetes mellitus: a case-control study in a single tertiary care center.
作者信息
Alharbi Khalid Khalaf, Al-Sulaiman Abdulrahman Mohammed, Shedaid Khalid Muath Bin, Al-Shangiti Ali M, Marie Mohammed, Al-Sheikh Yazeed A, Ali Khan Imran
机构信息
From the Department of Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia.
From the Department of Medical and Molecular Virology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
出版信息
Ann Saudi Med. 2019 Sep-Oct;39(5):309-318. doi: 10.5144/0256-4947.2019.309. Epub 2019 Oct 3.
BACKGROUND
Gestational diabetes mellitus (GDM) is a metabolic disease in pregnancy that causes carbohydrate intolerance and hyper-glycemia. Genome-wide association studies and meta-analyses have found that the single nucleotide polymorphisms (SNPs) rs1387153 and rs10830963 of the melatonin receptor 1B ( MTNR1B) gene are associated with GDM. No studies on the MTNR1B gene effect on GDM have been performed in Saudis, other Arabs, or other Middle Eastern populations.
OBJECTIVES
Investigate the association of genotype or allele frequencies of the two SNPs with GDM and with clinical parameters related to GDM.
DESIGN
Case-control study.
SETTINGS
Tertiary care center, Riyadh.
PATIENTS AND METHODS
We recruited 400 pregnant Saudi women ages 18-45 years (200 were diagnosed with GDM, and 200 were healthy controls). Biochemical assays were performed, and rs1387153 and rs10830963 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis and real-time polymerase chain reaction with TaqMan genotyping.
MAIN OUTCOME MEASURES
The association of MTNR1B gene (rs1387153 and rs10830963 polymorphisms) with GDM and with biochemical parameters related to GDM.
SAMPLE SIZE
200 GDM cases and 200 non-GDM controls.
RESULTS
Differences in allele frequencies for GDM vs non-GMD were statistically significant or nearly significant for both SNPs after adjustment for age and body mass index. In a logistic regression analysis, genotype TT was positively associated with post-prandial blood glucose (P=.018), but other associations were not statistically significant.
CONCLUSION
The odds ratios for the associations between the rs1387153 and rs10830963 SNPs and GDM exceeded 1.5-fold, which is higher than typically reported for diseases with complex genetic background. These effect sizes for GDM suggest pregnancy-specific factors related to the MTNR1B risk genotypes.
LIMITATIONS
Only two SNPs were studied.
CONFLICT OF INTEREST
None.
背景
妊娠期糖尿病（GDM）是一种妊娠期间的代谢性疾病，可导致碳水化合物不耐受和高血糖。全基因组关联研究和荟萃分析发现，褪黑素受体1B（MTNR1B）基因的单核苷酸多态性（SNP）rs1387153和rs10830963与GDM相关。在沙特人、其他阿拉伯人或其他中东人群中，尚未进行关于MTNR1B基因对GDM影响的研究。
目的
研究这两个SNP的基因型或等位基因频率与GDM以及与GDM相关临床参数之间的关联。
设计
病例对照研究。
地点
利雅得的三级医疗中心。
患者和方法
我们招募了400名年龄在18 - 45岁的沙特孕妇（200名被诊断为GDM，200名作为健康对照）。进行了生化检测，并通过聚合酶链反应 - 限制性片段长度多态性分析以及使用TaqMan基因分型的实时聚合酶链反应分析rs1387153和rs10830963多态性。
主要观察指标
MTNR1B基因（rs1387153和rs10830963多态性）与GDM以及与GDM相关生化参数之间的关联。
样本量
200例GDM病例和200例非GDM对照。
结果
在调整年龄和体重指数后，两个SNP的GDM组与非GDM组的等位基因频率差异具有统计学意义或接近统计学意义。在逻辑回归分析中，基因型TT与餐后血糖呈正相关（P = 0.018），但其他关联无统计学意义。
结论
rs1387153和rs10830963 SNP与GDM之间关联的优势比超过1.5倍，高于通常报道的具有复杂遗传背景疾病的水平。这些GDM的效应大小表明与MTNR1B风险基因型相关的妊娠特异性因素。
局限性
仅研究了两个SNP。
利益冲突
无。
Zotero 插件