A substitution mutation in LRP8 gene is significantly associated with susceptibility to familial myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a multifactorial disease caused by the suspension of blood circulation in a part of the myocardium. Understanding the genetic basis of MI can provide insight regarding the pathogenesis of the disease. The aim of this study was to investigate the association between pathogenic mutations and early-onset MI in five families with familial MI and without common MI risk factor. METHODS: Patients with MI younger than 50 years with family history of MI and without common diagnostic criteria (obesity, diabetes, familial hypercholesterolemia, opium/alcohol use) were evaluated for pathogenic mutations by whole exome sequencing (WES) and mutation was confirmed by polymerase chain reaction (PCR)-Sanger sequencing. RESULTS: The c.2855G > A missense mutation with homozygous autosomal recessive inheritance was identified in low-density lipoprotein receptor-related protein 8 (LRP8) gene in all patients of a family. CONCLUSION: The c.2855G > A (R952Q) mutation in LRP8 gene in homozygous state could be considered as a possible etiology of early-onset familial MI.

Nonlinear association between serum testosterone levels and coronary artery disease in Iranian men.

Previous studies have shown controversial results about the role of androgens in coronary artery disease (CAD). We performed this study to examine and compare the relationship between androgenic hormones and CAD using conventional linear statistical techniques as well as novel non-linear approaches. The study was conducted on 502 consecutive men who were referred for selective coronary angiography at Tehran Heart Center due to different indications. We studied the relationship between androgenic hormones and CAD by using the generalized linear models, generalized additive models, and neural networks. Free testosterone (fT), total testosterone (tT) and dehydroepiandrosterone sulfate levels in patients with significant CAD versus normal individuals were 6.69 +/- 3.20 pg/ml, 16.60 +/- 6.66 nm/l, and 113.38 +/- 72.9 microg/dl versus 7.12 +/- 3.58 pg/ml, 15.82 +/- 7.26 nm/l, and 109.03 +/- 68.19 microg/dl, respectively (P > 0.05). The Generalized linear models was unable to show any significant relationship between androgenic hormones and CAD, while generalized additive model and neural networks supported the significant effect of androgenic hormones on CAD. This finding suggests a nonlinear association of tT levels with CAD: lower levels have a preventive effect on CAD, whereas higher values increase the risk of CAD. Emphasizing the non-linearity of the variables may provide new insight into the possible explanation of the effect of androgenic hormones on CAD.

Genetic analysis of early onset familial coronary artery diseases.

INTRODUCTION: Coronary artery diseases (CAD) are the most common causes of death. Myocardial infarction (MI) is a complex multifactorial and the most severe type of CAD. Early onset MI in a first-degree relative could be defined as an independent risk factor for CAD. This study was performed to investigate the genetic cause of early onset familial CAD. MATERIAL AND METHODS: In this study, the genetic cause of familial CAD was investigated in patients with a family history of CAD who underwent angiography before the age of 50 years. The patients did not have any diagnostic criteria for familial hypercholesterolemia, diabetes, or obesity, and also they were not opium or alcohol users. Whole exome sequencing in probands was performed and mutation was confirmed by PCR and Sanger sequencing. RESULTS: In our studied population, the c.501G>C (p.K167N) mutation in the OLR1 gene was identified in a family. Mutation was confirmed by PCR and Sanger sequencing in the homozygous state (GG) in patients. Healthy individuals in this family were heterozygous (GC) and homozygous (CC). CONCLUSIONS: This finding suggests that the OLR1 gene could be a possible cause of early onset familial MI. Considering that parents of all affected individuals had a consanguineous marriage, it is important to perform carrier screening and genetic counseling in this family and their close relatives as a prevention strategy in populations at risk.

Specific Antivenom Ability in Neutralizing Hepatic and Renal Changes 24 Hours after Latrodectus dahli Envenomation.

BACKGROUND: Latrodectism, a syndrome caused by Latrodectus genus, is one of the clinical problems that occur predominantly in north east of Iran. Nowadays antivenom therapy has become the most useful treatment for animal bites; however there is still a controversy about route and time of antivenom administration in spider bite. The aim of the present study was to determine the efficacy of specific antivenom in neutralizing hepatic and renal symptoms 24 h after Latrodectus dahli envenomation. METHODS: We selected a group of male New Zealand white rabbits, weighing 2±0.3 kg. The L. dahli venom (0.5 mg/kg) was injected subcutaneously. Specific antivenom (2.5 ml, I.V) was injected 24 h following venom injection. Blood sampling was performed before and 24 h after venom injection, as well within 24, 48 and 72 h after antivenom administration. Serum levels of (aspartate amino transferase (AST) alanine amino transferase (ALT), alkaline phosphatase (ALP), urea, bilirubin, creatinine and albumin were determined in all the sam. RESULTS: Latrodectus dahli venom caused significant increase (P< 0.05) in all foresaid serum parameters. Antivenom reversed the AST, ALP, creatinine, urea and bilirubin to normal levels, but failed about ALT level, also non-significant decrease was observed in albumin levels. CONCLUSION: Antivenom administration 24 h after venom injection can greatly reverse symptoms caused by venom. Future studies in human beings should be conducted to assess the protection against the specific-Latrodectus anti-venom.