21 research outputs found
Stevens-Johnson syndrome and toxic epidermal necrolysis: an update on pharmacogenetics studies in drug-induced severe skin reaction
Stevens-Johnson syndrome and toxic epidermal necrolysis are severe, life-threatening drug reactions involving skin and membranes mucous, which are associated with significant morbidity and mortality and triggered, especially by drug exposure. Different studies have demonstrated that drug response is a multifactorial character and that the interindividual variability in this response depends on both environmental and genetic factors. The last ones have a relevant significance. In fact, the identification of new specific genetic markers involved in the response to drugs, will be of great utility to establish a more personalized therapeutic approach and to prevent the appearance of these adverse reactions. In this review, we summarize recent progresses in the Pharmacogenetics studies related to Stevens-Johnson syndrome/toxic epidermal necrolysis reporting the major genetic factors identified in the last years as associated with the disease and highlighting the use of some of these genomic variants in the clinical practice
MicroRNA genetic variations: association with type 2 diabetes.
Abstract 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 in Systemic Lupus Erythematosus: Contribution to Disease Phenotype
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
Common polymorphisms in MIR146a, MIR128a and MIR27a genes contribute to neuropathy susceptibility in type 2 diabetes.
Abstract Diabetic polyneuropathy (DPN) and cardiovascular
autonomic neuropathy (CAN) are common type 2
diabetes complications with a large inter-individual variability
in terms of clinical manifestations and severity. Our
aim was to evaluate a possible involvement of genetic
polymorphisms in miRNA regions in the susceptibility to
DPN and CAN. Nine polymorphisms in miRNA genes
were studied in a sample of 132 type 2 diabetes patients
(T2D) analysed for DPN and 128 T2D patients analysed for
CAN. A genotype–phenotype correlation analysis was
performed. The T allele of rs11888095 single nucleotide
polymorphism (SNP) in MIR128a was significantly associated
with a higher risk (ORadj = 4.89, Padj = 0.02),
whereas the C allele of rs2910164 SNP in MIR146a
was associated with a lower risk to develop DPN
(ORadj = 0.49, Padj = 0.09), respectively. A multivariate
logistic regression analysis confirmed that both SNPs
contribute to DPN (p\0.001 and p = 0.01 for MIR128a
and MIR146a, respectively). MIR128a SNP significantly
contributed also to DPN score (p = 0.026). Rs895819 SNP
in MIR27a was significantly associated with a higher risk
to develop early CAN (Padj = 0.023 and ORadj = 3.43).
The rs2910164 SNP in MIR146a showed a protective
effect respect to early CAN (Padj = 0.052, ORadj = 0.32)
and to confirmed CAN (Padj = 0.041, ORadj = 0.13). The
same SNP resulted significantly associated with a lower
CAN score and a higher E/I (p = 0.002 and p = 0.003,
respectively). In conclusion, we described associations of
MIR128a and MIR146a SNPs with DPN susceptibility and
of MIR146a and MIR27a SNPs with CAN susceptibility.
This is the first study showing that genetic variability in
miRNA genes could be involved in diabetic neuropathies
susceptibility
Association analysis between TRAF3IP2, STAT4, PSORS1C1 and PTPN2 polymorphisms and response to TNF-inhibitors treatment in RA patients.
<p>Association analysis between TRAF3IP2, STAT4, PSORS1C1 and PTPN2 polymorphisms and response to TNF-inhibitors treatment in RA patients.</p
Demographic and clinical data of 171 patients with Rheumatoid Arthritis included in the study.
<p>Demographic and clinical data of 171 patients with Rheumatoid Arthritis included in the study.</p
Association between analyzed polymorphisms and response to Etanercept treatment in RA patients.
<p>Association between analyzed polymorphisms and response to Etanercept treatment in RA patients.</p