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The association between eating behavior and polymorphisms in GRIN2B, GRIK3, GRIA1 and GRIN1 genes in people with type 2 diabetes mellitus

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Abstract

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/m2 (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/m2 (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 (ORadj) = 0.77 (95% CI 0.63–0.93), padj = 0.0077], rs1805476 in GRIN2B [ORadj = 1.25 (95% CI 1.03–1.51), padj = 0.0240], and rs2195450 in GRIA1 [ORadj = 1.35 (95% CI 1.02–1.79), padj = 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 HbA1c (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.

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Abbreviations

AIC:

Akaike information criterion

AMPA:

d,l-Alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid

CKD-EPI:

Chronic kidney disease epidemiology collaboration

CNS:

Central nervous system

DEBQ:

Dutch Eating Behavior Questionnaire

GRIA1 :

Gene of glutamate receptor, ionotropic, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate 1

GRIK3 :

Gene of glutamate receptor, ionotropic, kainate 3

GRIN1 :

Gene of glutamate receptor, ionotropic, N-methyl d-aspartate 1

GRIN2B :

Gene of glutamate receptor, ionotropic, N-methyl d-aspartate 2B

NMDA:

N-Methyl-d-aspartate

NMDAR:

N-Methyl-d-aspartate receptor

TG:

Triglyceride

T2D:

Type 2 diabetes

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Acknowledgements

The study was partially supported by Russian Foundation for Basic Research (Grant No. 20-013-00261) and Federal Agency for Scientific Organizations, bioresource collection support program (Agreement No. 007-030164/2).

Author information

Conceptualization, TM; Data curation, DA; Formal analysis, OM; Funding acquisition, TM; Investigation, OK and GK; Methodology, OK; Project administration, OM; Supervision, TM; Validation, OM; Writing—original draft, OK; Writing—review & editing, DA.

Correspondence to Diana S. Avzaletdinova.

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Kochetova, O.V., Avzaletdinova, D.S., Korytina, G.F. et al. The association between eating behavior and polymorphisms in GRIN2B, GRIK3, GRIA1 and GRIN1 genes in people with type 2 diabetes mellitus. Mol Biol Rep (2020). https://doi.org/10.1007/s11033-020-05304-x

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Keywords

  • Tatar population
  • Single nucleotide polymorphism
  • Susceptibility genes
  • Type 2 diabetes
  • Glutamatergic genes