Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, 71 October Avenue, Ufa, Russia, 450054.
Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of Healthcare Ministry of the Russian Federation, 3 Lenin St., Ufa, Russia, 45008.
Mol Biol Rep. 2020 Mar;47(3):2035-2046. doi: 10.1007/s11033-020-05304-x. Epub 2020 Feb 10.
Excess body weight is the main risk factor of type 2 diabetes. Recent studies have shown that psychological and behavioral factors affect weight. Additionally, emerging evidence indicates that polymorphisms of neurotransmitter genes can impact eating behavior. The aim of this study was to detect the associations between SNPs in glutamatergic system genes and type 2 diabetes in the ethnic group of Tatars origin living in the Republic of Bashkortostan (Russian Federation). In our case-control cross-sectional study, 501 patients with type 2 diabetes (170 men and 331 women, 60.9 ± 9.2 years old (mean ± SD), BMI 30.9 ± 3.9 kg/m (mean ± SD) of Tatar ethnicity, and a control group of 420 Tatars (170 men and 250 women, 56.3 ± 11.6 years old (mean ± SD), BMI 24.4 ± 4.3 kg/m (mean ± SD), were genotyped for five SNPs in four glutamatergic genes (GRIN2B, GRIK3, GRIA1, GRIN1). Three SNPs were associated with type 2 diabetes: rs7301328 in GRIN2B [odds ratio adjusted for age, sex and BMI (OR) = 0.77 (95% CI 0.63-0.93), p = 0.0077], rs1805476 in GRIN2B [OR = 1.25 (95% CI 1.03-1.51), p = 0.0240], and rs2195450 in GRIA1 [OR = 1.35 (95% CI 1.02-1.79), p = 0.0340]. Regression analysis revealed that rs1805476 in GRIN2B was associated with LDL level, glomerular filtration rate, BMI (p = 0.020, p = 0.012 and p = 0.018, respectively). The SNP rs7301328 in GRIN2B was associated with triglyceride levels and HbA (p = 0.040, p = 0.023, respectively). These associations were not significant after Bonferroni correction. We found the association between rs534131 in GRIK3, rs2195450 in GRIA1, rs1805476 in GRIN2B and diabetic retinopathy (p = 0.005, p = 0.007, p = 0.040, respectively); rs7301328 in GRIN2B was associated with hypertension (p = 0.025) and cerebrovascular disease (p = 0.013). The association between rs534131 of GRIK3, rs2195450 of GRIA1 genes and diabetic retinopathy remained significant after Bonferroni correction. The SNPs rs6293 in GRIN1 was significantly associated with eating behavior in patients with type 2 diabetes (p = 0.01). Our results demonstrate that polymorphic variants of glutamatergic genes are associated with eating behavior and diabetic complications in Tatar ethnic group residing in the Republic of Bashkortostan. We detected novel associations of the polymorphic loci in GRIN1 (rs6293) gene with external eating behavior in type 2 diabetes patients, GRIK3 (rs534131) and GRIA1 (rs2195450) genes with diabetic retinopathy.
超重是 2 型糖尿病的主要危险因素。最近的研究表明，心理和行为因素会影响体重。此外，新出现的证据表明，神经递质基因的多态性会影响进食行为。本研究旨在检测谷氨酸能系统基因中的 SNPs 与居住在俄罗斯巴什科尔托斯坦共和国的鞑靼人族群 2 型糖尿病之间的关联。在我们的病例对照横断面研究中，501 例 2 型糖尿病患者（170 名男性和 331 名女性，60.9 ± 9.2 岁（平均值 ± 标准差），BMI 30.9 ± 3.9 kg/m （平均值 ± 标准差），为鞑靼族，对照组为 420 名鞑靼人（170 名男性和 250 名女性，56.3 ± 11.6 岁（平均值 ± 标准差），BMI 24.4 ± 4.3 kg/m （平均值 ± 标准差），对四个谷氨酸能基因（GRIN2B、GRIK3、GRIA1、GRIN1）中的五个 SNPs 进行了基因分型。三个 SNP 与 2 型糖尿病相关：GRIN2B 中的 rs7301328 [调整年龄、性别和 BMI 的比值比（OR）=0.77（95%CI 0.63-0.93），p=0.0077]、GRIN2B 中的 rs1805476 [OR=1.25（95%CI 1.03-1.51），p=0.0240]和 GRIA1 中的 rs2195450 [OR=1.35（95%CI 1.02-1.79），p=0.0340]。回归分析显示，GRIN2B 中的 rs1805476 与 LDL 水平、肾小球滤过率、BMI 相关（p=0.020、p=0.012 和 p=0.018）。GRIN2B 中的 rs7301328 与甘油三酯水平和 HbA 相关（p=0.040、p=0.023）。经 Bonferroni 校正后，这些关联不再显著。我们发现 rs534131 与 GRIK3、rs2195450 与 GRIA1、rs1805476 与 GRIN2B 之间的关联与糖尿病视网膜病变相关（p=0.005、p=0.007、p=0.040）；GRIN2B 中的 rs7301328 与高血压（p=0.025）和脑血管疾病（p=0.013）相关。经 Bonferroni 校正后，GRIK3 中的 rs534131 和 GRIA1 中的 rs2195450 与糖尿病视网膜病变之间的关联仍然显著。GRIN1 中的 rs6293 与 2 型糖尿病患者的进食行为显著相关（p=0.01）。我们的研究结果表明，谷氨酸能基因的多态性与居住在巴什科尔托斯坦共和国的鞑靼族群的进食行为和糖尿病并发症有关。我们检测到了 GRIN1（rs6293）基因多态性与 2 型糖尿病患者的外部进食行为、GRIK3（rs534131）和 GRIA1（rs2195450）基因与糖尿病视网膜病变之间的新关联。
