Maturity onset diabetes of the young (MODY) is a congenital form of diabetes characterized by onset at a young age and a primary defect in pancreatic-β-cell function. Currently, 14 subtypes of MODY are known, and each is associated with mutations in a specific gene: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1. The most common subtypes of MODY are associated with mutations in the genes GCK, HNF1A, HNF4A, and HNF1B. Among them, up to 70% of cases are caused by mutations in GCK and HNF1A. Here, an analysis of 14 MODY genes was performed in 178 patients with a MODY phenotype in Western Siberia. Multiplex ligation-dependent probe amplification analysis of DNA samples from 50 randomly selected patients without detectable mutations did not reveal large rearrangements in the MODY genes. In 38 patients (37% males) among the 178 subjects, mutations were identified in HNF4A, GCK, HNF1A, and ABCC8. We identified novel potentially causative mutations p.Lys142*, Leu146Val, Ala173Glnfs*30, Val181Asp, Gly261Ala, IVS7 c.864 −1G>T, Cys371*, and Glu443Lys in GCK and Ser6Arg, IVS 2 c.526 +1 G>T, IVS3 c.713 +2 T>A, and Arg238Lys in HNF1A.

This review addresses the contribution of some genes to the phenotype of familial hypercholesterolemia. At present, it is known that the pathogenesis of this disease involves not only a pathological variant of low-density lipoprotein receptor and its ligands (apolipoprotein B, proprotein convertase subtilisin/kexin type 9 or low-density lipoprotein receptor adaptor protein 1), but also lipids, including sphingolipids, fatty acids, and sterols. The genetic cause of familial hypercholesterolemia is unknown in 20%–40% of the cases. The genes STAP1 (signal transducing adaptor family member 1), CYP7A1 (cytochrome P450 family 7 subfamily A member 1), LIPA (lipase A, lysosomal acid type), ABCG5 (ATP binding cassette subfamily G member 5), ABCG8 (ATP binding cassette subfamily G member 8), and PNPLA5 (patatin like phospholipase domain containing 5), which can cause aberrations of lipid metabolism, are being evaluated as new targets for the diagnosis and personalized management of familial hypercholesterolemia.

The main functions of adipose tissue are thought to be storage and mobilization of the body’s energy reserves, active and passive thermoregulation, participation in the spatial organization of internal organs, protection of the body from lipotoxicity, and ectopic lipid deposition. After the discovery of adipokines, the endocrine function was added to the above list, and after the identification of crosstalk between adipocytes and immune cells, an immune function was suggested. Nonetheless, it turned out that the mechanisms underlying mutual regulatory relations of adipocytes, preadipocytes, immune cells, and their microenvironment are complex and redundant at many levels. One possible way to elucidate the picture of adipose-tissue regulation is to determine genetic variants correlating with obesity. In this review, we examine various aspects of adipose-tissue involvement in innate immune responses as well as variants of immune-response genes associated with obesity.

The APPL1 gene encodes a protein mediating the cross-talk between adiponectin and insulin signaling. Recently, it was found that APPL1 mutations can cause maturity onset diabetes of the young, type 14. Here, an analysis of APPL1 was performed in patients with a maturity-onset diabetes of the young (MODY) phenotype, and prevalence of these mutations was estimated in a Russian population, among type 2 diabetes mellitus (T2DM) and MODY patients. Whole-exome sequencing or targeted sequencing was performed on 151 probands with a MODY phenotype, with subsequent association analysis of one of identified variants, rs11544593, in a white population of Western Siberia (276 control subjects and 169 T2DM patients). Thirteen variants were found in APPL1, three of which (rs79282761, rs138485817, and rs11544593) are located in exons. There were no statistically significant differences in the frequencies of rs11544593 alleles and genotypes between T2DM patients and the general population. In the MODY group, AG rs11544593 genotype carriers were significantly more frequent (AG vs. AA + GG: odds ratio 1.83, confidence interval 1.15–2.90, p = 0.011) compared with the control group. An association of rs11544593 with blood glucose concentration was revealed in the MODY group. The genotyping data suggest that rs11544593 may contribute to carbohydrate metabolism disturbances.

Investigate the association of rs17465637 gene MIAF3 (1q41), rs1376251 gene TAS2R50 (12p13), rs4804611 gene ZNF627 (19p13), rs619203 gene ROS1 (6q22), rs1333049 (9p21), rs10757278 (9p21), rs2549513 (16q23), rs499818 (6p24) associated with myocardial infarction available from the international genome-wide studies with sudden cardiac death (SCD) in a case–control study. A sample of SCD cases (n = 285) was formed using the WHO criteria; the control sample (n = 421) was selected according to sex and age. DNA was isolated by phenol–chloroform extraction from the myocardial tissue of SCD cases and blood of control cases. The groups were genotyped for the selected SNPs by real-time PCR using TaqMan probes (Applied Biosystems, United States). No statistically significant differences in the genotype and allelic frequencies of studied single nucleotide polymorphisms between sudden cardiac death cases and control were detectable in general group. By separating the groups of sex and age differences in the genotype frequencies of rs1333049, rs10757278 and rs499818 are statistical significance. Genotypes CC of rs1333049 and GG of rs10757278 are associated with an increased sudden cardiac death risk in men (p = 0.019, OR = 1.7, 95% CI 1.1–2.8; p = 0.011, OR = 1.8, 95% CI 1.2–2.8, respectively). Genotype AG of rs499818 is associated with an increased sudden cardiac death risk in the women over 50 years old (p = 0.009, OR = 2.4, 95% CI 1.3–4.6). Polymorphisms rs1333049 and rs10757278 are associated with SCD in men and rs499818 in the women aged over 50 years.

The present study aimed to analyze possible associations of rs7412 and rs429358 of the APOE gene with lipid profile parameters, the risk of myocardial infarction, and death in the mostly white population of Western Siberia (Russia). The study population was selected from a sample surveyed within the framework of the Health, Alcohol and Psychosocial Factors In Eastern Europe (HAPIEE) study (9360 subjects, age 53.8 ± 7.0 years, males/females 50/50). PCR was conducted with fluorescence detection according to the TaqMan principle on a real-time PCR machine. The frequency of a minor allele (C) of rs429358 was 0.13, and the frequency of a minor allele (T) of rs7412 was 0.09. In our study, the woman with the rare ɛ1/ɛ4 genotype had substantial aberrations in blood lipid levels. In Kaplan–Meier curves, statistically significant differences were revealed in the prognosis of survival within the subgroup of females who had a myocardial infarction (p = 0.0006): the prognosis was worse for carriers of the ɛ2/ɛ2 genotype and for ɛ4/ɛ4 carriers. Survival analysis regarding deaths from all causes showed (p = 0.0238) that female carriers of the ɛ2/ɛ4 genotype had a worse prognosis than did carriers of other genotypes. Thus, in the population of Western Siberia (Russia), we confirmed statistically significant associations between rs7412 & rs429358 genotypes and lipid profile parameters.