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Introduction Sudden cardiac death is an important cause of mortality in the general population. It represents an important challenge for clinicians, often being the only symptom of a broad spectrum of cardiac pathologies and inherited heart conditions. Early repolarization syndrome and Brugada syndrome are part of the wider “J-wave” syndrome, which may also include the short QT syndrome as a third factor of an ionic channel imbalance in the arrhythmogenic landscape. Case presentation We describe the case of a woman struck down by sudden cardiac death, with short QT and early repolarization, in which we found an extremely rare and putatively pathogenic heterozygous variant in the SCN10A gene. Variants involving SCN10A , which encodes a voltage-gated sodium channel, were already associated with alterations of cardiac conduction parameters and the cardiac rhythm disorder, thereby influencing the cardiac physiology and predisposing to arrhythmia. Conclusion We underline the role of genetic predisposition to sudden cardiac death and, for the first time, suggest a possible environmental effect, such as a pharmacological therapy in the setting of sudden death, with the purpose to increase awareness in clinical practice.

Background Although metabolic syndrome (MetSyn) or albuminuria (MA) most often occurs in concomitance in Type 2 Diabetes Mellitus patients (T2DM), their mode of interaction in increasing the risk of low glomerular filtration rate (GFR) has been poorly investigated. Objective We evaluated in a cohort of 1659 T2DM patients the relationship between MetSyn and MA in modulating the risk for low GFR. The risk of developing low GFR by graded number of MetSyn traits was also evaluated. Methods This was a cross-sectional study where 1659 T2DM patients were studied. Low GFR was defined as estimated-GFR (e-GFR) Results e-GFR progressively decreased from 91 ± 25 of patients MetSyn−MA−, to 82 ± 27 of patients MetSyn−MA+, 81 ± 24 of patients MetSyn+MA− and 76 ± 30 ml min−1 × 1.73 m−2 of patients MetSyn+MA+ (adjusted p Conclusions MetSyn or MA has an additive effect in increasing the risk of having low GFR in patients with T2DM. Furthermore, e-GFR is negatively affected by graded number of MetSyn traits independently of albuminuria.

Background Insulin resistance has a role in diabetic kidney complications. The K121Q (lysine to glutamine substitution at amino acid 121, encoded by single-nucleotide polymorphism rs1044498) variant of the ectonucleotide pyrophosphatase/phosphodiesterase gene ( ENPP1) has been associated with insulin resistance and related vascular complications in patients with type 2 diabetes (T2D) in many, although not all, studies. This study investigated whether the ENPP1 Q121 variant modulates the risk of decreased glomerular filtration rate (GFR) in patients with T2D. Study Design Cross-sectional study. Setting & Participants 2 diabetes units from Italy (in Gargano and Padua) and 1 from the United States (Boston, MA) recruited a total of 1,392 patients with T2D. Predictor The ENPP1 Q121 variant. Measurements Estimated GFR from serum creatinine, urinary albumin excretion, blood pressure, hemoglobin A 1c , triglycerides, total cholesterol, and high-density lipoprotein cholesterol. Outcomes Decreased GFRs (ie, estimated GFR 2 ). Results In the Gargano and Boston populations, according to the dominant model of inheritance, Q121 carriers (ie, individual with either KQ or QQ alleles) had an increased risk of decreased GFR: odds ratios (ORs) of 1.69 (95% confidence interval [CI], 1.1 to 2.6) and 1.50 (95% CI, 1.0 to 2.2), respectively. In the Padua set, the association was in the same direction, but did not reach formal statistical significance (OR, 1.77; 95% CI, 0.7 to 4.5). When the 3 studies were pooled, Q121 carriers showed an increased risk of decreased GFR (OR, 1.58; 95% CI, 1.2 to 2.1; P = 0.002). Also, pooled mean differences in absolute GFRs were different across genotype groups, with Q121 carriers showing lower GFRs compared with KK individuals ( P = 0.04). Limitations P values not approaching a genome-wide level of significance. Conclusions Our data suggest that patients with T2D carrying the ENPP1 Q121 variant are at increased risk of decreased GFR.

Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling and, when overexpressed, plays a role in insulin resistance (Ahmad et al. 1997). We identified, in the 3' untranslated region of the PTP1B gene, a 1484insG variation that, in two different populations, is associated with several features of insulin resistance: among male individuals, higher values of the insulin resistance HOMA(IR) index (P=.006), serum triglycerides (P=.0002), and total/HDL cholesterol ratio (P=.025) and, among female individuals, higher blood pressure (P=.01). Similar data were also obtained in a family-based association study by use of sib pairs discordant for genotype (Gu et al. 2000). Subjects carrying the 1484insG variant showed also PTP1B mRNA overexpression in skeletal muscle (6,166 plus minus 1,879 copies/40 ng RNA vs. 2,983 plus minus 1,620; P.01). Finally, PTP1B mRNA stability was significantly higher (P.01) in human embryo kidney 293 cells transfected with 1484insG PTP1B, as compared with those transfected with wild-type PTP1B. Our data indicate that the 1484insG allele causes PTP1B overexpression and plays a role in insulin resistance. Therefore, individuals carrying the 1484insG variant might particularly benefit from PTP1B inhibitors, a promising new tool for treatment of insulin resistance (Kennedy and Ramachandran 2000).