Role of KCNJ11 Gene Polymorphisms and Risk of Type 2 Diabetes Mellitus

Arterial hypertension and type 2 diabetes mellitus are the most widespread comorbid pathologies. The coexistence of these disorders accelerates the development of micro- and macrovascular complications, considerably increases the cardiovascular risk, as well as the risk of stroke and end stage renal disease. The synergism of these two pathologies is caused by the unity of pathogenetic mechanisms. Genetic predisposition also contributes to the development of both pathologies. It is well known that blockade of the renin-angiotensin system slows down the development of type 2 diabetes mellitus and also reduces the frequency of cardiovascular or kidney events in patients with these disorders. Gene polymorphisms of the reninangiotensin system are thoughtfully studied in the context of cardiovascular disease development. Currently, the role of gene polymorphisms in the development of carbohydrate disorders is not established, however, there is a high probability of their influence and importance. The purpose of review is to analyze the accumulated data on the effects of the renin-angiotensin system gene polymorphisms on the development of arterial hypertension and type 2 diabetes mellitus.

Download Full-text

Risk of type 2 diabetes mellitus in the Kyrgyz population in the presence of ADIPOQ (G276T), KCNJ11 (Glu23Lys), TCF7L2 (IVS3C>T) gene polymorphisms

Terapevticheskii arkhiv ◽

10.17116/terarkh2017891040-47 ◽

2017 ◽

Vol 89 (10) ◽

pp. 40-47

Author(s):

Zh T Isakova ◽

E T Talaibekova ◽

D A Asambaeva ◽

A S Kerimkulova ◽

O S Lunegova ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gene Polymorphisms ◽

Tcf7l2 Gene ◽

Genotype Combination ◽

Adipoq Gene ◽

Kcnj11 Gene ◽

Kyrgyz Population

Aim. To analyze the association of genotype combinations of the polymorphic markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population. Subjects and methods. The investigation enrolled 23 Kyrgyz people, of whom there were 114 patients with T2DM and 109 without T2DM (a control group). T2DM was diagnosed in accordance with the WHO criteria (1999). The genotypes of ADIPOQ (G276T), KCNJ11 (Glu23Lys), and TCF7L2 (IVS3C>T) gene polymorphisms were identified using the restriction fragment length polymorphism analysis. Results. When typing at the polymorphic loci G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene, the development of T2DM in the Kyrgyz population was associated with the T allele (odds ratio (OR), 1.68; p=0.025), the heterozygous G276T genotype (OR 1,8; p=0.036) in the ADIPOQ gene; the 23Lys allele (OR, 1.62; p=0.019) in the KCNJ11 gene; a two-locus genotype combination in the genes ADIPOQ/KCNJ11: G276T/Glu23Lys (OR, 4.88; p=0.0013), G276G/Lys23Lys (OR, 4.65; p=0.019), G276T/Glu23Glu (OR, 3.10; p=0.022), a two-locus genotype combination in the genes ADIPOQ/TCF7L2: G276T/СС (OR, 1.97; p=0.04); two-locus genotype combinations in the genes KCNJ11/TCF7L2: Lys23Lys/CC (ОR, 2.65; p=0.042), Glu23Lys/CT (OR, 3.88; p=0.027); and a three-locus genotype combination in the genes ADIPOQ/KCNJ11/TCF7L2: G276T/Glu23Lys/CT (OR, 14.48; p=0.02). Conclusion. The development of T2DM in the Kyrgyz population is genetically determined by ADIPOQ (G276T) gene, KCNJ11 (Glu23Lys), and TCF7L (IVS3C>T) gene polymorphisms with the predisposing value of the T allele of the heterozygous G276T genotype in the ADIPOQ gene; the 23Lys allele in the KCNJ1 gene; as well as by genotype combinations in the genes ADIPOQ/KCNJ11 (G276T/Glu23Lys, G276G/Lys23Lys, G276T/Glu23Glu); ADIPOQ/TCF7L2 (G276T/SS); KCNJ11/TCF7L2 (Lys23Lys/CC, Glu23Lys/CT); ADIPOQ/KCNJ11/TCF7L2 (G276T/Glu23Lys /CT). The IVS3C>T locus in the TCF7L2 gene is not independently statistically significantly associated with the development of T2DM; however, its predisposing effect has been identified in its combination with the variant genotypes of the polymorphic loci G276T in the ADIPOQ gene and Glu23Lys in the KCNJ11 gene.

Download Full-text