Aggarwal Parul, Agarwal Nutan, Das Nibhriti, Dalal Krishna
Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India.
Int J Appl Basic Med Res. 2016 Jan-Mar;6(1):31-7. doi: 10.4103/2229-516X.174006.
Numerous genes have been reported in relation with gestational diabetes mellitus (GDM), but the findings were not consistently replicated across populations, or there have been no detailed studies on them. Previous literatures suggested that, out of all angiotensin converting enzyme (ACE) gene polymorphisms, only ACE insertion/deletion (I/D) gene polymorphism has a strong association with GDM in Asian Indian women.
This study was devoted to evaluate the association of four single nucleotide polymorphisms (SNPs) ACE A240T, C1237T, G2350A and I/D with GDM and Type 2 diabetes mellitus.
This study recruited 105 GDM cases, 119 Type 2 diabetes mellitus subjects and 120 controls. PCR-RFLP was used for identifying genotypes of ACE A240T, C1237T and G2350A and PCR was performed in the case of ACE I/D.
Significant associations of ACE SNP's, C1237T, and G2350A with GDM were observed. Haplotype analysis revealed the remarkably significant evidence of association with SNP combination ACE A240T, C1237T, G2350A, and I/D with GDM patients (P = 0.024). Individuals possessing haplotype "TTAI" (frequency 30% in GDM and 0 in controls) derived from these SNPs had 185 fold increased risk of developing GDM (95% of confidence interval: 11.13-3102.15), which was highest when compared with other 15 haplotypes.
Shorter-range haplotypes were also significant, but the only consistently associated alleles were found to be in ACE C1237T, G2350A, and I/D. These results suggested that the variant in close proximity to ACE C1237T, G2350A and/or I/D modulates susceptibility to GDM and noninsulin dependent diabetes mellitus in Indian women.
已有众多基因被报道与妊娠期糖尿病（GDM）相关，但研究结果在不同人群中未能得到一致重复，或者尚未对这些基因进行详细研究。既往文献表明，在所有血管紧张素转换酶（ACE）基因多态性中，只有ACE插入/缺失（I/D）基因多态性与亚洲印度女性的GDM有强关联。
本研究旨在评估4种单核苷酸多态性（SNP），即ACE A240T、C1237T、G2350A和I/D与GDM及2型糖尿病的关联。
本研究招募了105例GDM患者、119例2型糖尿病患者和120例对照。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法鉴定ACE A240T、C1237T和G2350A的基因型，对于ACE I/D则进行PCR检测。
观察到ACE SNP的C1237T和G2350A与GDM存在显著关联。单倍型分析显示，SNP组合ACE A240T、C1237T、G2350A和I/D与GDM患者存在非常显著的关联证据（P = 0.024）。拥有源自这些SNP的单倍型“TTAI”（在GDM中的频率为30%，在对照中为0）的个体患GDM的风险增加了185倍（95%置信区间：11.13 - 3102.15），与其他15种单倍型相比风险最高。
较短范围的单倍型也具有显著性，但唯一始终相关的等位基因存在于ACE C1237T、G2350A和I/D中。这些结果表明，靠近ACE C1237T、G2350A和/或I/D的变异调节了印度女性对GDM和非胰岛素依赖型糖尿病的易感性。
