Correction to: Clopidogrel Pharmacogenetics in Iranian Patients Undergoing Percutaneous Coronary Intervention.

The original version of this article unfortunately contained a typo in the co-author name.

Clopidogrel Pharmacogenetics in Iranian Patients Undergoing Percutaneous Coronary Intervention.

Clopidogrel is used in patients with coronary syndromes and at risk of thrombotic events or receiving percutaneous coronary intervention (PCI) for reducing heart attack and stroke. Here we present genotype and phenotype study of Iranian patients undergoing PCI treated with clopidogrel during a 6-month period of follow-up; common variants of CYP2C19, CYP3A5, CYP3A4, and ABCB1 genes were determined as well as the patients' cardiovascular outcomes to find out the effect of these variants individually and in combination. 388 individuals receiving PCI were enrolled in this study. Different pretreatment doses of clopidogrel were prescribed under the interventional cardiologists' guidance. The patients were followed for a duration of 1 month, and 6 months. Six SNPs were selected for genotyping including CYP2C19*2 (c.681G > A), CYP2C19*3 (c.636G > A), CYP2C19*17 allele (c.-806C > T), ABCB1 (c.3435C > T), CYP3A5 (c.6986A > G), and CYP3A4 (c.1026 + 12G > A). The mean loading dose was 600 mg/day in 267 (68.8%) individuals, 300 mg/day in 121 (31.2%). 8 patients had cardiovascular events such as thrombosis, unstable angina, and non-STEMI. The studied alleles and genotypes were in Hardy-Weinberg equilibrium. None of the SNPs individually were significantly associated with outcome events. Our results indicate that combinations of different alleles of genes are involved in pharmacokinetic variability and joint factors are important; this means that genotyping and analysis of an individual variant may not be as straightforward in risk assessment and pharmacogenetics. This highlights the importance of personalized medicine in risk assessment and treatment.

Genotypic effect of a mutation of the MYBPC3 gene and two phenotypes with different patterns of inheritance.

BACKGROUND: MYBPC3 mutations have been described in dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). A mutation, c.3373G>A, has been reported to cause autosomal recessive form of HCM. Here, we report that this mutation can cause autosomal dominant form of DCM. METHODS: Next-generation sequencing using targeted panel of a total of 23 candidate genes and following Sanger sequencing was applied to detect causal mutations of DCM. Computational analyses were also performed using available software tools. In silico structural and functional analyses including protein modeling and prediction were done for the mutated MYBPC3 protein. RESULTS AND CONCLUSION: Targeted sequencing showed one variant c.3373G>A (p.Val1125Met) in the studied family following autosomal dominant inheritance. Computational programs predicted a high score of pathogenicity. Secondary structure of the region surrounding p.Val1125 was changed to a shortened beta-strand based on prediction of I-TASSER and Phyre2 servers with high confidence value for the mutation. cMyBP-C protein was modeled to 3dmkA. Our findings suggest that one single mutation of MYBPC3 may have different effects on the cellular mechanisms based of its zygosity. Various factors might be considered for explaining this phenomenon. This gene may have an important role in Iranian DCM and HCM patients.

Assessment of pubertal development in Iranian girls.

OBJECTIVE: We estimated pubertal development of 7,493 normal Iranian girls aged 6 to 20 years in a cross-sectional study. METHODS: Pubertal stages were assessed according to Tanner. The mean ages to achieve secondary sexual characteristics as well as the mean age at menarche were estimated. Weight and height were measured and body mass index (BMI) was calculated. Reference curves for different breast stages and menarche were constructed. The percentiles for attaining each stage were compared to data proposed by Tanner. FINDINGS: The mean age at breast bud stage (B2) was 10.10, pubic hair stage (P2) was 9.83, and menarche age was 12.55 years. The anthropometric variables were interpreted in different maturity stages. The mean age at attainment of puberty was compared with those of other populations. CONCLUSION: Not only the onset of puberty in Iranian girls but also the duration of puberty is similar to data from most other countries. A lower age limit for the definition of precocious puberty than the traditional 8 years is documented for Iranian girls. However, it should be noted that considering the rate of evolution of pubertal findings is more important than the age of their appearance.

Vitamin D insufficiency among children and adolescents living in Tehran, Iran.

Vitamin D is important for calcium absorption and skeletal growth. Vitamin D insufficiency (VDI) is a prevalent health problem in children. A study was performed to determine the prevalence of VDI in healthy children living in Tehran, Iran. In a cross-sectional study, 963 students (424 boys and 539 girls) aged 7-18 years were selected by random sampling. Serum 25-hydroxyvitamin D (25-OHD), calcium, alkaline phosphatase and phosphorus were measured. VDI was defined as serum 25-OHD <20 ng/ml. Prevalence of VDI was 53.6% in girls and 11.3% in boys. VDI in female students was about five times more common than males (p < 0.000001). VDI in children and adolescent girls is a health problem not only for these age-groups but also for the next generation to come. Encouraging girls to have more sun exposure, fortification of foods and prescription of supplemental vitamin D are recommended.