A Genetic Association Study of a Specific Gene and Severe Form of Resorption in the Edentulous Mandible in the Egyptian Population.

PURPOSE: To investigate for the first time in Egypt and the Middle East the relationship between a specific gene and the presence of severely resorbed edentulous mandibular ridges in a sample of the Egyptian population. MATERIALS AND METHODS: The study was conducted on 50 subjects divided into case and control groups according to the residual ridge height. Saliva was used as a convenient source of DNA in the dental clinic. A certain genetic variation (1772C>T) in an important gene related to bone healing (hypoxia-inducible factor-1 alpha [HIF1-α] gene) was selected. The genetic variation 1772C>T is a single nucleotide polymorphism (SNP) that occurs when corresponding sequences of DNA from different individuals differ at one base. Then, we have 2 forms of the gene (2 alleles): C and T. SNPs typically have 3 genotypes; in this study, they are the CC, CT, and TT genotypes. Polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) was the method performed for genotyping. The statistical significance of the results was evaluated by the Chi-square test and Fisher Exact test. RESULTS: A statistically significant difference in the distribution of the TT genotype between both groups was detected with p-value = 0.049. There was also a difference in the distribution of the CC and CT genotypes, but it was not statistically significant, since the p-values were 0.733 and 0.145, respectively. The T alleles were more abundant in the case group, while the control group showed more frequency of the C allele with no statistical significance. CONCLUSION: The TT genotype of the 1772C>T polymorphism of HIF1-α gene is related to the presence of severely atrophied residual ridges in completely edentulous Egyptians. This can be used as a marker to predict the future condition of the ridge using saliva samples. Further studies on larger scale are recommended.

The Effect of Genetic Variants of SLC22A2 (rs662301 and rs315978) on the response to Metformin in type 2 Saudi diabetic patients.

PURPOSE: To investigate the allelic and genotypic frequencies of the two genetic variations, NC_000006.12: g.160275887C > T (rs662301) and NC_000006.12:g.160231826 T > C (rs315978), in the SLC22A2 gene among the Saudi population. The primary goal is to elucidate potential associations with these genetic variations and the response to metformin therapy over 6 months to enhance our knowledge of the genetic basis of Type 2 Diabetes Mellitus (T2DM) and its clinical management in the Saudi population. MATERIALS/METHODS: 76 newly diagnosed T2DM patients, aged 30 to 60, of both sexes and Saudi origin, were treated with metformin monotherapy. Blood samples were collected before and after 6 months of therapy,80 healthy individuals were included as controls. Genomic DNA was extracted. Genotyping of the SLC22A2 genetic variations was performed using TaqMan® SNP Genotyping Assays. Binary logistic regression was utilized to evaluate how certain clinical parameters influence T2DM concerning the presence of SLC22A2 gene variants. RESULTS: Among these patients, 73.3 % were responders, and 26.7 % were non-responders. For these variants, no statistically significant differences in genotype or allele frequencies were observed between responders and non-responders (p = 0.375 and p = 0.384 for rs662301; p = 0.473 and p = 0.481 for rs315978, respectively). For the SLC22A2 variant rs662301, the C/C genotype was significantly associated with increased T2DM risk with age and elevated HbA1c levels. Similarly, rs315978 revealed higher T2DM susceptibility and HbA1c elevation in C/C genotype carriers, specifically with advancing age compared to individuals with C/T and T/T genotypes. CONCLUSION: The study offers insights into the genetic landscape of T2DM in Saudi Arabia. Despite the absence of significant associations with treatment response, the study suggests potential age-specific associations, this highlights the complexity of the disease. This research underscores the necessity for expanded research, considering diverse populations and genetic factors, to develop personalized treatment approaches. This study serves as a foundation for future investigations into the Saudi population, recognizing the need for a larger sample size.

Quality of life in children with Down syndrome and its association with parent and child demographic characteristics: Parent-reported measures.

BACKGROUND: This study aims to explore the association between the quality of life (QoL) in children with Down syndrome (DS) and its relationship with demographic characteristics of both parents and children. The investigation encompasses five domains: physical and psychological well-being, autonomy and parental relationship, social well-being, and peers, as well as school and the learning environment. METHOD: An online questionnaire, the KIDSCREEN-27, was used to measure the QoL of 112 families with DS in Saudi Arabia, referred to as "Parent-Reported Measures." Descriptive statistics were analyzed using the Statistical Package for Social Sciences. RESULTS: The study found that the QoL of children with DS showed high scores in the psychological well-being, autonomy, parental relations, school, and learning environment domains. However, the physical and social well-being and peer domains had lower scores, although still considered "good scores." Family income had a positively significant influence on all QoL domains. Specifically, higher family income was associated with better QoL outcomes, except for social well-being. Parental age was found to influence psychological well-being, while parental education and the relationship between the parent and child influenced social well-being. Lastly, the child's gender was found to have an impact on the school and learning environment domain. CONCLUSION: The study highlights the importance of understanding the impact of the demographic variability of children with DS and their parents on the QoL of their children. It emphasizes the need to address the needs of families with lower incomes and the importance of parental education and relationships with their children in improving social well-being. The findings could aid policymakers and healthcare providers in improving the QoL for families with children who have DS.

Identification of a de novo LRP1 mutation in a Saudi family with Tetralogy of Fallot.

BACKGROUND: Tetralogy of Fallot (TOF) is a rare, complex congenital heart defect caused by genetic and environmental interactions that results in abnormal heart development during the early stages of pregnancy. Genetic basis of TOF in Saudi populations is not yet studied. Therefore, the objective of this study is to screen for the molecular defects causing TOF in Saudi patients. METHODS: A family with non-syndromic TOF was recruited from the Western region of Saudi Arabia. Whole exome sequencing (WES) was performed on the proband and her parents. The identified candidate variant was verified by sanger sequencing. Also, different computational biology tools were used to figure out how candidate variants affect the structure and function of candidate protein involved in TOF. RESULTS: A novel heterozygous de novo mutation in LRP1 (p. G3311D) gene was identified in the index case. Also, this variant was absent in the in-house exome sequencing data of 80 healthy Saudi individuals. This variant was predicted to be likely pathogenic, as it negatively affects the biophysical chemical properties and stability of the protein. Furthermore, functional biology data from knock out mouse models confirms that molecular defects in LRP1 gene leads to cardiac defects and lethality. This variant was not previously reported in both Arab and global population genetic databases. CONCLUSION: The findings in this study postulate that the LRP1 variant has a role in TOF pathogenesis and facilitate accurate diagnosis as well as the understanding of underlying molecular mechanisms and pathophysiology of the disease.

Effect of cypermethrin on the postnatal development of the medulla oblongata and the possible protective role of melatonin in albino rats.

Previous studies have shown that cypermethrin (CYP), a broad spectrum pesticide has a teratogenic effect on rat offspring born to an exposed dam with no information on its effect on the development of the brain. To the best of our knowledge, this research is the first attempt to study the postnatal development medulla oblongata of rat offspring exposed to CYP during the perinatal period and the possible neuroprotective role of melatonin. The offspring of treated female rats were organized into control, melatonin (1 mg/kg/day orally); CYP (12 mg/kg/day orally); and CYP/melatonin groups. The mothers received treatments from day 6 of gestation until day 21 after birth. At Postnatal days 7 and 21, the animals were sacrificed and their medulla oblongata was removed and subjected to histological, immunohistochemical, and electron microscopic studies. CYP induced neuronal degeneration by chromatolysis and pyknosis. Nuclear changes, cytoplasmic vacuolation, damage mitochondria, and breakdown of RER were also detected. Reduction of microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), and oligodendrocyte transcription factor expressions and increment of glial fibrillary acidic protein expression in the medulla oblongata of the developing rats were observed. On the other hand, melatonin led to an obvious improvement of the injured medulla oblongata tissues and ameliorating the damaging effects of CYP. In conclusion, melatonin has protected rats against CYP-induced histopathological and immunohistochemical changes. This may be due to the protection of MAP-2, conservation of MBP, an increment of oligodendrocytes, and alleviation of astrogliosis.

The clinical significance of serum miRNA-224 expression in hepatocellular carcinoma.

AIM OF THE STUDY: Micro-ribonucleic acids (miRNA) are small single stranded RNA molecules. They act as key regulators of several cellular processes such as proliferation, apoptosis, tumor differentiation, invasion and metastasis. Hepatocellular carcinoma (HCC) represents the most common primary liver cancer. miRNA-224 is an oncomiR that is highly upregulated in HCC tissues. The aim of the present study was to measure the relative expression of circulating miRNA-224 in the serum of patients with HCV-related liver cirrhosis and HCC and to assess its usefulness in the diagnosis of HCC. MATERIAL AND METHODS: Forty-eight patients were classified into two groups: 24 HCV-related HCC patients (HCC group), and 24 HCV-related liver cirrhosis patients (LC group). A third group included 24 healthy volunteers (control group). Clinical examination, imaging studies and routine laboratory investigations, including serum α-fetoprotein (AFP), were done. Quantification of serum miRNA-224 expression was performed using real time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The relative expression of serum miRNA-224 was significantly higher in HCC patients compared to LC patients and healthy control subjects. Its level correlated positively with the serum concentration of AFP and with Barcelona Clinic Liver Cancer (BCLC) stage of HCC. By combining miRNA-224 relative expression with AFP, their diagnostic sensitivity, specificity and accuracy increased significantly (95.0%, 92.1% and 93.2%, respectively) compared with either of the two markers alone in discriminating HCC from liver cirrhosis. CONCLUSIONS: Serum miRNA-224 relative expression may aid in the diagnosis of HCC. Better diagnostic performance is obtained if miRNA-224 is combined with other tumor markers such as AFP.