Vitamin D Receptor FokI, ApaI, and TaqI Polymorphisms in Lead Exposed Subjects From Saudi Arabia

Vitamin D receptor (VDR) gene polymorphisms were reported to influence blood lead levels (BLL) and the response of subjects to the symptoms of lead toxicity. However, no studies have been conducted in the Saudi Arabian population which has unique ethnicity and socio-demographic features. This study examined the polymorphisms in exon 2 (allele 1) and intron 8 (allele 2 and allele 3) of VDR gene and their relation to BLLs. As per the CDC guidelines, the recruited lead-exposed workers (N = 130) were categorized to two groups viz., low BLL group (<10 μg/dL) and high BLL group (>10 μg/dL). The low BLL group had a mean BLL of 4.37 μg/dL, while the high BLL group had levels of 18.12 μg/dL (p < 0.001). Overall, the genetic variants, TC and CC in the VDR FokI were significantly associated with a risk of lead toxicity and the allele “C” was a risk factor (p = 0.00026). Furthermore, the TT genotype of VDR ApaI significantly increased the risk of developing lead poisoning (p = 0.0006). The VDR TaqI SNP was not significantly associated with lead toxicity. The highest BLLs for VDR FokI-CC, VDR ApaI-GG, and VDR TaqI-TT genotypes from High BLL group were 18.42, 15.26, and 18.75 μg/dL, respectively. Older age (51–60 years) was found to be a significant confounding factor for BLLs (p = 0.012). Additional studies in larger sample sizes are needed to firmly establish the role of VDR genotypes and genetic susceptibility to lead poisoning

Lead Exposure: A Summary of Global Studies and the Need for New Studies from Saudi Arabia

Lead poisoning (plumbism) can cause irreversible genetic and reproductive toxicity, hematological effects, neurological damage, and cardiovascular effects. Despite many efforts to minimize lead poisoning, it continues to be a major health concern in many developing and developed countries. Despite efforts to control lead exposure and toxicity, serious cases of lead poisoning increasingly occur as a result of higher vehicular traffic and industrialization. The biomarkers for identification of genetic susceptibility to a particular disease are useful to identify individuals who are at risk for lead poisoning. Although many such studies have been taken up elsewhere, very few studies were performed in Saudi Arabia to assess susceptibility to lead poisoning. This indicates an urgent need for testing of susceptible individuals. The present paper was planned to understand the genetic susceptibility to lead toxicity in the various population studies conducted worldwide and also to correlate it with the current scenario in Saudi Arabia. Such studies are necessary for appropriate precautions in terms of diet and avoiding exposure to be used in order to prevent adverse health effects

Haplotype Analyses of DNA Repair Gene Polymorphisms and Their Role in Ulcerative Colitis

<div><p>Ulcerative colitis (UC) is a major clinical form of inflammatory bowel disease. UC is characterized by mucosal inflammation limited to the colon, always involving the rectum and a variable extent of the more proximal colon in a continuous manner. Genetic variations in DNA repair genes may influence the extent of repair functions, DNA damage, and thus the manifestations of UC. This study thus evaluated the role of polymorphisms of the genes involved in DNA repair mechanisms. A total of 171 patients and 213 controls were included. Genotyping was carried out by ARMS PCR and PCR-RFLP analyses for <i>RAD51</i>, <i>XRCC</i>3 and <i>hMSH2</i> gene polymorphisms. Allelic and genotypic frequencies were computed in both control & patient groups and data was analyzed using appropriate statistical tests. The frequency of ‘A’ allele of <i>hMSH</i>2 in the UC group caused statistically significant increased risk for UC compared to controls (OR 1.64, 95% CI 1.16–2.31, <i>p</i> = 0.004). Similarly, the CT genotype of <i>XRCC</i>3 gene was predominant in the UC group and increased the risk for UC by 1.75 fold compared to controls (OR 1.75, 95% CI 1.15–2.67, <i>p</i> = 0.03), further confirming the risk of ‘T’ allele in UC. The GC genotype frequency of <i>RAD</i>51 gene was significantly increased (<i>p</i> = 0.02) in the UC group (50.3%) compared to controls (38%). The GC genotype significantly increased the risk for UC compared to GG genotype by 1.73 fold (OR 1.73, 95% CI 1.14–2.62, <i>p</i> = 0.02) confirming the strong association of ‘C’ allele with UC. Among the controls, the SNP loci combination of <i>hMSH</i>2:<i>XRCC</i>3 were in perfect linkage. The GTC and ACC haplotypes were found to be predominant in UC than controls with a 2.28 and 2.93 fold significant increase risk of UC.</p></div

Surfactant-driven optimization of iron-based nanoparticle synthesis: a study on magnetic hyperthermia and endothelial cell uptake

This work examines the effect of changing the ratio of different surfactants in single-core iron-based nanoparticles with respect to their specific absorption rate in the context of magnetic hyperthermia and cellular uptake by human umbilical vein endothelial cells (HUVEC). Three types of magnetic nanoparticles were synthesized by separately adding oleic acid or oleylamine or a mixture of both (oleic acid/oleylamine) as surfactants. A carefully controlled thermal decomposition synthesis process led to monodispersed nanoparticles with a narrow size distribution. Spherical-shaped nanoparticles were mainly obtained for those synthesized with oleic acid, while the shape changed upon adding oleylamine. The combined use of oleic acid and oleylamine as surfactants in single-core iron-based nanoparticles resulted in a substantial saturation magnetization, reaching up to 140 A m2 kg−1 at room temperature. The interplay between these surfactants played a crucial role in achieving this high magnetic saturation. By modifying the surface of the magnetic nanoparticles using a mixture of two surfactants, the magnetic fluid hyperthermia heating rate was significantly improved compared to using a single surfactant type. This improvement can be attributed to the larger effective anisotropy achieved through the modification with both (oleic acid/oleylamine). The mixture of surfactants enhances the control of interparticle distance and influences the strength of dipolar interactions, ultimately leading to enhanced heating efficiency. Functionalization of the oleic acid-coated nanoparticles with trimethoxysilane results in the formation of a core–shell structure Fe@Fe3O4, showing exchange bias (EB) associated with the exchange anisotropy between the shell and the core. The biomedical relevance of our synthesized Fe@Fe3O4 nanoparticles was demonstrated by their efficient uptake by human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. This remarkable cellular uptake highlights the potential of these nanoparticles in biomedical applications

<i>hMSH</i>2 genotypic distribution in UC compared to healthy controls.

<p><i>hMSH</i>2 genotypic distribution in UC compared to healthy controls.</p

Allele frequency distributions of <i>hMSH</i>2 <i>XRCC</i>3 <i>RAD</i>51 (G135C) in UC and healthy controls.

<p>Allele frequency distributions of <i>hMSH</i>2 <i>XRCC</i>3 <i>RAD</i>51 (G135C) in UC and healthy controls.</p

Haplotype association with response.

<p>Haplotype association with response.</p

<i>XRCC</i>3 genotypic distribution in patients with UC and healthy controls.

<p><i>XRCC</i>3 genotypic distribution in patients with UC and healthy controls.</p

Pairwise Linkage Disequilibrium estimates in controls and Ulcerative colitis group.

<p>Pairwise Linkage Disequilibrium estimates in controls and Ulcerative colitis group.</p