Lack of Evidence of the Role of APOA5 3’UTR Polymorphisms in Iranian Children and Adolescents with Metabolic Syndrome

BACKGROUND: Metabolic syndrome (MetS) is a complex and multifactorial disorder characterized by insulin resistance, dyslipidaemia, hyperglycemia, abdominal obesity, and elevated blood pressure. The apolipoprotein A5 (APOA5) gene variants have been reported to correlate with two major components of MetS, including low levels of high density lipoprotein cholesterol (HDL-C) and high levels of triglyceride. In the present study, we explored the associations between five single nucleotide polymorphisms (SNPs) of APOA5 gene and the MetS risk. METHODS: In a case-control design, 120 Iranian children and adolescents with/without MetS were genotyped by polymerase chain reaction-sequencing for these SNPs. Then, we investigated the association of SNPs, individually or in haplotype constructs, with MetS risk. RESULTS: The rs34089864 variant and H1 haplotype (harboring the two major alleles of rs619054 and rs34089864) were associated with HDL-C levels. However, there was no significant association between different haplotypes/individual SNPs and MetS risk. CONCLUSION: These results presented no association of APOA5 3’UTR SNPs with MetS. Further studies, including other polymorphisms, are required to investigate the involvement of APOA5 gene in the genetic susceptibility to MetS in the pediatric age group.

Absence of association between -1131T>C polymorphism in the apolipoprotein apoa5 gene and pediatric metabolic syndrome

In the present study, we evaluated the association of rs662799 variant of the APOA5gene with Metabolic syndrome [MetS] in a sample of children and adolescents from Isfahan. This case control study comprised 50 cases of MetS and 50 controls. Mismatched polymerase chain reaction-restriction fragment length polymorphism [mPCR-RFLP] was used to genotype -1131T>C polymorphism. No significant association was documented for APOA 5 genotypes with the measured laboratory parameters for CC, CT, and TT genotypes in the two groups studied. By logistic regression using a dominant model, the odds ratio [95% confidence interval 10 for the MetS was 0.38 [0.139-1.0350 and 0.29 [0.08-1.071 for the unadjusted and adjusted models, respectively. This study suggests that among studied children and adolescents, -1131T>C polymorphism in the APOA5gene may not be a major contributor to the MetS risk

G395R mutation of the sodium/iodide symporter [NIS] gene in patients with dyshormonogenetic congenital hypothyroidism

Considering the high prevalence of congenital hypothyroidism [CH] in Isfahan and its different etiologies in comparison with other countries, the high rate of parental consanguinity, and the role of NIS gene in permanent CH due to dyshormonogenesis, the aim of this study was to investigate the G395R mutation of the NIS gene in patients with permanent CH due to dyshormonogenesis. In this case-control study, patients diagnosed with permanent CH due to dyshormonogenesis during CH screening program were selected. Venous blood sample was obtained to determine the G395R mutations of NIS gene using polymerase chain reaction [PCR] sequencing method. In this study, 35 CH patients with permanent CH due to dyshormonogenesis and 35 neonates with normal screening results as a control group were studied. We did not find any changes of the mentioned mutation of NIS gene in the patients' group. Considering the findings of the current study, it seems that further studies with larger sample size and with consideration of other gene mutations such as pendrin and thyroglobulin are needed for more accurate conclusion

Evaluation of sensitivity and specificity of urine surviving as a new molecular marker in diagnosis of bladder tumors

Bladder cancer is one of the most common forms of cancers in the world. The current gold standards for its diagnosis are cystoscopy and urine cytology. Cystoscopy, a naked eye assessment of the bladder, is invasive, uncomfortable and costly with a great deal of personal variability in its results; while urine cytology has high specificity but low sensitivity, particularly for low-grade lesions. Therefore, there is a need for a molecular tumor marker assay capable of detecting bladder cancer with high sensitivity and specificity. A growing list of tumor markers in urine has been introduced so far, but neither of them has been able to replace the current diagnostic methods. Survivin, an inhibitor of apoptosis [IAP] capable of regulating both cell proliferation and apoptosis, has been recently defined as a universal tumor antigen and as the fourth most significant transcript expressed in human tumors. It has been reported to have 100% sensitivity and 95% specificity for detection of bladder cancer. In the present study, the sensitivity and specificity of survivin as a tumor marker in detecting new and recurrent cases of bladder cancer has been evaluated by nested RT-PCR technique. Our results revealed that survivin could be detected in most patients [11/13, sensitivity=0.84] as well as some healthy volunteers with no obvious sign of bladder cancer [6/13, specificity=0.53]. Also, in this work, for the first time, the presence of two alternatively spliced variants of survivin [survivin-2B and survivin-DEx3] urine is being reported. Interestingly, the presence of survivin-DEx3 was better correlated with malignant lesions of bladder compared to the survivin expression [sensitivity=0.84, specificity=0.92]