Our data confirm and strengthen the role of this variant.

MicroRNAs are small single-stranded molecules that have emerged as important genomic regulators in different pathways. Different studies have shown that they are implicated in the metabolism and glucose homeostasis, and therefore, they could also be involved in the pathogenesis of metabolic disorders such as type 2 diabetes (T2DM). The aim of this study was to verify whether genetic variations in candidate microRNA (miRNA or miR) genes could contribute to T2DM susceptibility. We have selected 13 miRNAs as candidate loci according to literature data and to a computational analysis. MicroRNA genes were analyzed by direct sequencing in a cohort of 163 Italian T2DM patients and 185 healthy controls. We identified 6 novel variants never described before and 9 SNPs already described in databases. Five newly identified variants were found only in the cases group. We performed a case/control association study to test the associations of particular alleles/genotypes of identified SNPs with the disease. Two polymorphisms were associated with T2DM susceptibility: in particular, the G allele of rs895819 in hsa-mir-27a has shown a significantly protective effect (OR = 0.58 and P = 0.008), while the G allele of rs531564 in hsa-mir-124a appears to be a risk allele (OR = 2.15, P = 0.008). This is the first report indicating that genetic polymorphisms in miRNA regions could contribute to T2DM susceptibility.

Genetic factors exert an important role in determining Systemic Lupus Erythematosus (SLE) susceptibility, interplaying with environmental factors. Several genetic studies in various SLE populations have identified numerous susceptibility loci. From a clinical point of view, SLE is characterized by a great heterogeneity in terms of clinical and laboratory manifestations. As widely demonstrated, specific laboratory features are associated with clinical disease subset, with different severity degree. Similarly, in the last years, an association between specific phenotypes and genetic variants has been identified, allowing the possibility to elucidate different mechanisms and pathways accountable for disease manifestations. However, except for Lupus Nephritis (LN), no studies have been designed to identify the genetic variants associated with the development of different phenotypes. In this review, we will report data currently known about this specific association.

Type 2 diabetes (T2DM) is a complex disease resulting from the contribution of both environmental and genetic factors. Recently, the list of genes implicated in the susceptibility to T2DM has substantially grown, also as a consequence of the great development of the genome-wide association studies in the last decade. Common polymorphisms in TCF7L2 gene have shown to have a strong effect with respect to many other involved genes. The aims of our study were to confirm the role of TCF7L2 in the susceptibility to T2DM in the Italian population and to investigate whether TCF7L2 genotypes also contribute to the clinical phenotypes variability and to diabetic complications development. Three TCF7L2 polymorphisms (rs7903146, rs7901695 and rs12255372) have been analyzed by allelic discrimination assays in a cohort of 154 Italian patients with T2DM and 171 healthy controls. A case-control association study and a genotype-phenotype correlation study have been carried out. Consistent with previous studies, all three SNPs showed a strong association with susceptibility to T2DM, both at genotypic (P = 0.003, P = 0.004 and P = 0.012) and at allelic level (P = 0.0004, P = 0.0004 and P = 0.003). Moreover, we observed associations between TCF7L2 variants and the following diabetic complications: diabetic retinopathy, cardiovascular disease and coronary artery disease. We also found a strong correlation between the rs7903146 and the presence of cardiovascular autonomic neuropathy (P = 0.02 with a high OR = 8.28). In conclusion, our study, in addition to confirming the involvement of TCF7L2 gene in the T2DM susceptibility, has shown that TCF7L2 genetic variability also contributes to the development of diabetic complications such as retinopathy and cardiovascular autonomic neuropathy.

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease with complex pathogenesis in which genes and environmental factors are involved. We aimed at analyzing previously identified loci associated with SLE or with other autoimmune and/or inflammatory disorders (STAT4, IL10, IL23R, IRAK1, PSORS1C1, HCP5, MIR146a, PTPN2, ERAP1, ATG16L1, IRGM) in a sample of Italian SLE patients in order to verify or confirm their possible involvement and relative contribution in the disease.Materials and methodsTwo hundred thirty-nine consecutive SLE patients and 278 matched healthy controls were enrolled. Study protocol included complete physical examination, and clinical and laboratory data collection. Nineteen polymorphisms were genotyped by allelic discrimination assays. A case-control association study and a genotype-phenotype correlation were performed.ResultsSTAT4 was the most associated gene [P = 3×10−7, OR = 2.13 (95% CI: 1.59–2.85)]. IL10 confirmed its association with SLE [rs3024505: P = 0.02, OR = 1.52 (95% CI: 1.07–2.16)]. We describe a novel significant association between HCP5 locus and SLE susceptibility [rs3099844: P = 0.01, OR = 2.06 (95% CI: 1.18–3.6)]. The genotype/phenotype correlation analysis showed several associations including a higher risk to develop pericarditis with STAT4, and an association between HCP5 rs3099844 and anti-Ro/SSA antibodies.ConclusionsSTAT4 and IL10 confirm their association with SLE. We found that some SNPs in PSORS1C1, ATG16L1, IL23R, PTPN2 and MIR146a genes can determine particular disease phenotypes. HCP5 rs3099844 is associated with SLE and with anti-Ro/SSA. This polymorphism has been previously found associated with cardiac manifestations of SLE, a condition related with anti-Ro/SSA antibodies. Thus, our results may provide new insights into SLE pathogenesis.