Adiponectin gene single-nucleotide polymorphisms in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease

Mìžnarodnij Endokrinologìčnij Žurnal

M. Gorshunska¹  Yu. Karachentsev²  T. Tyzhnenko³  V. Роltorak³  A. Gladkih³  O. Plohotnichenko³  Zh. Leshchenko³  A. Pochernyaev³  T. Mishchenko³  N. Kravchun³  N. Krasova³  L. Atramentova³  I. Dunaeva³ 

[1] Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine;State Institution “V. Danilevsky Institute of Endocrine Pathology Problems of the National Academy of Medical Sciences of Ukraine”, Kharkiv, UkraineKharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine;State Institution “V. Danilevsky Institute of Endocrine Pathology Problems of the National Academy of Medical Sciences of Ukraine”, Kharkiv, Ukraine;

关键词: adiponectin gene;    single nucleotide polymorphism;    genotype frequencies;    type 2 diabetes mellitus;    nonalcoholic fatty liver disease;    insulin resistance;   

DOI  :  10.22141/2224-0721.13.4.2017.106646

来源: DOAJ

【 摘 要 】

Background. It is generally believed that environmental and genetic factors interact with the formation of nonalcoholic fatty liver disease (NAFLD) phenotype and determine its progression. Both NAFLD and type 2 diabetes (T2D) are heterogeneous diseases with common pathogenic pathways. Adiponectin is an adipokine, which increases the sensitivity of hepatocytes and muscle to insulin, modulates energy homeostasis, glucose/lipid metabolism, and inflammatory response. A number of significant adiponectin gene polymorphisms are known in this area. The purpose of the study was to evaluate the possible association between two adiponectin gene (ADIPOQ) variants, +276 G/T (rs1501299) and –11391 G/A (rs17300539), and susceptibility to NAFLD in T2D patients of Ukrainian population. Materials and methods. Case-control study included a total of 155 persons with T2D (males/females: 77/78, age 54.55 ± 0.73 years, T2D duration 6.66 ± 0.49 years, body mass index 32.20 ± 0.43 kg/m2, waist/hip circumference 0.98 ± 0.01 m, HbA1c 7.26 ± 0.11 %) for biochemical characteristics (lipid profile, non-esterified fatty acids (NEFA), insulin, total adiponectin, etc.), including 90 T2D patients with NAFLD, 245 — with rs1501299 genotyping, 155 — with rs17300539 genotyping, and 51 sex and age-matched control subjects. The +276 G/T and –11391 G/A were determined by polymerase chain reaction — restriction fragment length polymorphism method with endonucleases Mva1269I (BsmI) and MspI (HpaII). Insulin resistance (IR) was assessed using homeostasis model assessment (HOMA) algorithm and as adipose IR (Adipo-IR, NEFAxinsulin). Unpaired Student’s t test, c2 test and Spearman’s rank order were used. To predict the probabilities of genetic risk in NAFLD, the odds ratio (OR) and 95% confidence interval (CI) were calculated. Results. T2D patients were characterized by overweight and obesity, which were more significant in the presence of NAFLD (p < 0.01). It was accompanied by an increase in НОМА-IR (p < 0.05) and triglycerides (p < 0.001) levels. We found that Adipo-IR was higher in patients with T2D as compared to the controls (p < 0.001), and this index was significantly increased in T2D patients with NAFLD in contrast to obesity-matched persons without NAFLD (190.18 ± 22.15 vs 133.32 ± 13.58 mmol/L·pmol/L, p < 0.02), with negative correlation between Adipo-IR and adiponectin level in T2D patients with NAFLD only (rs = –0.350, p = 0.021). Stratification of non-NAFLD patients by +276G/T genotype suggests the prevalence of GT- and TT-genotypes. Thus, the rs1501299 G-allele increased the risk of NAFLD in comparison with T-allele (OR = 4.44, 95% CI = 2.89–6.81, p < 0.05). We also found a significant difference in the frequency of –11391G/A between T2D and control groups, but not between the patients with and without NAFLD. We observed that the haplotype of GT/GG had been more common in T2D with NAFLD, and twice less often detected in patients without hepatic disease (33 and 16.49 %, respectively, p < 0.05). Conclusions. We can recommend Adipo-IR index as a predictive marker for the NAFLD development and the indicator for therapy success in T2D patients. We established new genetic markers (rs1501299 G-allele, rs17300539 and rs1501299 GG/GG and GT/GG haplotypes, respectively) for the risk of NAFLD development in T2D patients.

【 授权许可】

Unknown