The effect of homozygous deletion of the BBOX1 and Fibin genes on carnitine level and acyl carnitine profile.

BACKGROUND: Carnitine is a key molecule in energy metabolism that helps transport activated fatty acids into the mitochondria. Its homeostasis is achieved through oral intake, renal reabsorption and de novo biosynthesis. Unlike dietary intake and renal reabsorption, the importance of de novo biosynthesis pathway in carnitine homeostasis remains unclear, due to lack of animal models and description of a single patient defective in this pathway. CASE PRESENTATION: We identified by array comparative genomic hybridization a 42 months-old girl homozygote for a 221 Kb interstitial deletions at 11p14.2, that overlaps the genes encoding Fibin and butyrobetaine-gamma 2-oxoglutarate dioxygenase 1 (BBOX1), an enzyme essential for the biosynthesis of carnitine de novo. She presented microcephaly, speech delay, growth retardation and minor facial anomalies. The levels of almost all evaluated metabolites were normal. Her serum level of free carnitine was at the lower limit of the reference range, while her acylcarnitine to free carnitine ratio was normal. CONCLUSIONS: We present an individual with a completely defective carnitine de novo biosynthesis. This condition results in mildly decreased free carnitine level, but not in clinical manifestations characteristic of carnitine deficiency disorders, suggesting that dietary carnitine intake and renal reabsorption are sufficient to carnitine homeostasis. Our results also demonstrate that haploinsufficiency of BBOX1 and/or Fibin is not associated with Primrose syndrome as previously suggested

Polymorphism of Pro12Ala in the peroxisome proliferator-activated receptor 2 gene in Iranian diabetic and obese subjects

Background: Peroxisome proliferator-activated receptor 2 (PPAR2) is a nuclear receptor that regulates adipocyte differentiation, lipid metabolism, and insulin sensitivity. The aim of this study was to investigate the association between the Pro12Ala single nucleotide polymorphism (SNP) at the PPAR2 gene and type II diabetes (T2DM) and obesity in an Iranian population. Methods: The genomic DNA of the 312 subjects included four groups: (1) nonobese with type II diabetes, (2) obese without type II diabetes, (3) obese with type II diabetes, and (4) nondiabetic nonobese controls. The Pro12Ala polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Frequencies of the Ala allele in obese subjects were significantly different from those control subjects (odds ratio [OR], 2.358; 95% confidence interval [CI], 1.101-5.05) (P = 0.025). In contrast, no significant association was detected between the Pro12Ala polymorphism and type II diabetes (OR, 0.652; 95% CI, 0.261-1.628). In all subjects, the Ala carriers had a higher body mass index (BMI) compared with the common allele. Conclusions: Our results showed that the Pro12Ala polymorphism in the PPAR2 gene is associated with obesity in Iranian subjects and the presence of the Ala allele could predict higher BMI. © 2009 Mary Ann Liebert, Inc

Effects of ramadan fasting on insulin-like growth factor-1 and low-density lipoprotein in healthy adults

Backgrounds & Purpose : Ramadan fasting is a unique cycle in which man should avoid eating and drinking. In many conditions such as plasma LDL and IGF-1 concentration, effects of prolonged & Ramadan fasting are different. This study was conducted to determine the effect of Ramadan fasting on LDL & IGF-1 and their correlations. Material & Methods: 132 healthy adult volunteers (60 women, 72 men) took part in this quasi-experimental study. All participants fasted for at least 25 days in the lunar month of Ramadan.The amount of serum IGF-1 was measured by radioimmunoassay 1 week before and on the 14th and 28th days of Ramadan. Statistical analysis with ANOVA, the Student's paired t-test, and Pearson's regression analysis were all carried out in this respect. Results : No significant change in the serum concentration of IGF-1 was found in men, women or the group during this study ,but serum level of LDL was decreased significantly. Conclusions: Ramadan fasting has no effect on plasma IGF-1, but it decreases plasma LDL significantl

Effect of Copper Sulfate on Expression of Endogenous L1 Retrotransposons in HepG2 Cells (Hepatocellular Carcinoma)

The long interspersed element-1 (LINE-1 or L1) constitutes approximately 17 of human genome. The expression of these elements is deregulated upon exposure to environmental exposures resulting to genomic instability and cancer promotion. The effect of copper as essential elements in regulation of L1 expression remained to be elucidated. Using non-cytotoxic concentrations of the copper, the expression of endogenous L1 was analyzed by qPCR after 6 days of copper pretreatment in human hepatocellular carcinoma cells (HepG2). The results indicated that the expression of active L1 elements are significantly downregulated at concentrations of 12.5, 25, and 50 μM (p < 0.005). Our data imply that low-level copper exposure may have a protective effect to suppress the induction of L1 activity and decrease incidence of cancer-associated L1 mutagenesis. If this achievement is confirmed by further studies, it can be applied in the long-term goals of cancer prevention. © 2015, Springer Science+Business Media New York

2q34-qter duplication and 4q34.2-qter deletion in a patient with developmental delay.

The 2q3 duplication and 4q3 deletion syndromes are two conditions with variable phenotypes including Pierre-Robin sequence (PRS), limb anomalies, congenital heart defects (CHD), developmental delays and intellectual disabilities. We describe a patient born to a mother with a balanced t(2; 4) translocation who combines both a 2q34-qter duplication and a 4q34.2-qter deletion through inheritance of the derivative chromosome 4 (der(4)). He showed developmental delay, growth retardation, hearing problems, minor facial and non-facial anomalies, such as bilateral fifth finger shortness and clinodactyly, but no PRS or CHD. The comparison of his features with those of 46 and 65 published cases of 2q3 duplication and 4q3 deletion, respectively, allows us to further restrict the size of the proposed critical intervals for PRS and CHD on chromosome 4