Sarcopenia associates with SNAP-25 SNPs and a miRNAs profile which is modulated by structured rehabilitation treatment

Background Sarcopenia is a loss of muscle mass and strength causing disability, morbidity, and mortality in older adults, which is characterized by alterations of the neuromuscular junctions (NMJs). SNAP-25 is essential for the maintenance of NMJ integrity, and the expression of this protein was shown to be modulated by the SNAP-25 rs363050 polymorphism and by a number of miRNAs. Methods We analysed these parameters in a cohort of sarcopenic patients undergoing structured rehabilitation. The rs363050 genotype frequency distribution was analyzed in 177 sarcopenic patients and 181 healthy controls (HC). The concentration of seven miRNAs (miR-451a, miR-425-5p, miR155-5p, miR-421-3p, miR-495-3p, miR-744-5p and miR-93-5p), identified by mouse brain miRNome analysis to be differentially expressed in wild type compared to SNAP-25± heterozygous mice, was analyzed as well by droplet digital PCR (ddPCR) in a subgroup of severe sarcopenic patients undergoing rehabilitation. Results The SNAP-25 rs363050 AA genotype was significantly more common in sarcopenic patients compared to HC (pc = 0.01); miR-451a was significantly up-regulated in these patients before rehabilitation. Rehabilitation modified miRNAs expression, as miR-155-5p, miR-421-3p, miR-451a, miR-425-5p, miR-744-5p and miR-93-5p expression was significantly up-regulated (p < 0.01), whereas that of miR-495-3p was significantly down-regulated (p < 0.001) by rehabilitation. Notably, rehabilitation-associated improvement of the muscle-skeletal SPPB score was significantly associated with the reduction of miR-451a expression. Conclusion These results support the hypothesis of a role for SNAP-25 in sarcopenia and suggest SNAP-25-associated miRNAs as circulatory biomarkers of rehabilitative outcome for sarcopenia.

Association between interleukin gene polymorphisms and susceptibility to gastric cancer in the Qinghai population

Objective To investigate the associations between interleukin (IL) gene polymorphisms and susceptibility to gastric cancer in the Qinghai population, China. Methods Patients with gastric cancer and cancer-free controls were enrolled into the study from Qinghai Provincial People’s Hospital between September 2016 and September 2018. Single nucleotide polymorphisms (SNPs) were genotyped with the Sequenom MassARRAY® SNP genotype system. The Hardy–Weinberg equilibrium in allele and genotype frequencies, and general characteristics between patients with gastric cancer and cancer-free controls, were evaluated using χ2-test. Potential associations between interleukin gene variants and the risk of gastric cancer were analysed by logistic regression. Results Among eight candidate SNPs, the allele and genotype frequency distribution of IL-1B rs1143634 polymorphism was significantly different between patients with gastric cancer ( n = 190) and cancer-free controls ( n = 186). The IL-1B rs1143634 GA genotype and IL-1B rs1143634 GA + AA genotype were associated with a reduced risk of gastric cancer, however, the remaining SNPs were not statistically associated with gastric cancer risk in the Qinghai population. Conclusion The IL-1B rs1143634 polymorphism might be associated with a decreased risk of gastric cancer, and may be a protective factor against gastric cancer.

Segregation Analysis of SSR, SNP, and AFLP Markers in F2 Population of Solanum lycopersicum × S. arcanum (Analisis Segregasi Marka SSR, SNP, dan AFLP pada Populasi F2 Persilangan Solanum lycopersicum × S. arcanum)

<p>Distorted marker segregation is a common phenomenon in interspecific cross of various crops. Previous mapping study of early<br />blight fungus (Alternaria solani) resistance loci showed 52% marker distortion in the genetic linkage map of 176 F2 progenies<br />derived from Solanum lycopersicum cv. Solentos × S. arcanum LA2157. The objectives of this study were to analyze in detail the<br />marker segregation in the map and to determine the cause of segregation distortion by calculating the allele and genotype<br />frequencies of each marker. Out of 371 mapped markers, 192 markers deviated from the expected Mendelian ratio of 1 : 2 : 1.<br />Distorted markers occurred in all chromosomes, ranging from 1% to 92%. Surplus of S. arcanum homozygotes contributed most<br />to the skewness (40%), followed by heterozygotes (18%), and S. lycopersicum homozygotes (5%). The allele frequencies of 152<br />markers deviated from the expected allele homogeneity frequency, indicating that their segregation might be affected by<br />gamethophytic selection. Sixty-one markers deviated from the expected F2 genotype frequency distribution, indicating that their<br />segregation might be influenced by zygotic selection. Thirty-seven of the distorted markers showed deviation from expected<br />frequencies of allele homogeneity and F2 genotype frequency distribution. Distorted markers can be retained in linkage analysis<br />since chromosomal regions containing distorted markers showed linkage with early blight fungus resistance loci. Further<br />identification of the mechanism contributing segregation distortion requires detailed and extensive mapping studies.</p>

Comparative analysis of HLA II allele and genotype frequency distribution in patients with type 1 diabetes mellitus and autoimmune thyroiditis

Aim. To compare HLA II allele and genotype frequency distribution in type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis (AIT) with that in isolated T1DM. Materials and Methods. A total of 92 T1DM patients were subdivided into two groups. The first group comprised 54 patients with established AIT comorbidity or elevation of anti-thyroid autoantibodies (ATA). Patients with isolated T1DM (ATA-negative) formed the second group. HLA-genotyping was performed by multiprimer PCR set for the three following genes: DRB1, DQA1 and DQВ1. Results. Prevalence of alleles DRB1*01, *03(017), *04, *07, *11 and genotypes 01/03, 01/04, 03/04 tends to be higher among patients with AIT comorbidity. The comorbidity group was also characterized by the trend towards higher prevalence of ?marker/marker? and ?marker/non-marker? combinations favouring the former variant. Conversely, ATA-negative patients exhibited trend for higher prevalence of ?non-marker/non-marker? combination. Conclusion. Statistically insignificant difference between HLA II alleles and genotypes in the two studied groups suggests that primary genetic factors are common in these two diseases. Plausibly, genes other than DRB1, DQA1 and DQВ1 determine the localization of the autoimmune process.

Polymorphic gene markers ILRA and IL2: population distinctions in association with diabetes mellitus

AIMS: In order to study type 1 diabetes mellitus associations, we conducted a comparative analysis of allele and genotype frequencydistribution of polymorphic markers rs41295061 and rs11594656 of IL2RA gene, which encodes -chain of interleukin-2 receptor, - and rs2069762, a marker of IL2, gene, encoding interleukin-2. MATERIALS AND METHODS: Experimental group included 451 patients with type 1 diabetes mellitus (DM); control group consistedof 306 healthy subjects (both groups were represented by ethnic Russians). Alleles and polymorphic markers were identified byreal-time amplification method. RESULTS: A comparative analysis of patients with type 1 DM and healthy control group did not show statistically significant differencesfrom the viewpoint of allele and genotype frequency distribution of polymorphic markers rs41295061, rs11594656 and rs2069762. This makes Russian patients considerably different from European ones where markers in question show substantialassociation with type 1 DM. CONCLUSIONS: A comparative analysis of allele and genotype frequency distribution of IL2-RA and IL2 genes polymorphic markersshowed population differences in association of these markers in Russian and European patients.