The Gln27Glu Polymorphism in β2-Adrenergic receptor gene is linked to hypertriglyceridemia, hyperinsulinemia and hyperleptinemia in Saudis

<p>Abstract</p> <p>Background</p> <p>β2-adrenoceptor (β2AR) gene polymorphism glutamine 27 glutamic acid (Gln27Glu) and Arg16Gly were reported to have an association with obesity and obesity related disorders in some population. We evaluated Gln27Glu polymorphism in the β2AR gene in obese Saudi populations to investigate the association of β2AR gene with obesity and other related metabolic parameters.</p> <p>Design</p> <p>We studied possible association of Gln27Glu in β2AR gene with body mass index (BMI), anthropometric measurements and other metabolic parameters. The β2AR gene polymorphism (Gln27Glu) was identified by sequencing PCR products representing locus of interest. Based on BMI, the subjects were divided into three groups, normal weight, overweight and obese. The genotype and allele frequency were calculated separately for each group.</p> <p>Results</p> <p>The allelic frequency of Glu27 did not differ amongst the three groups, though the Glu27 homozygote (Glu/Glu) were more in obese subjects and had higher concentration of triglyceride, leptin and insulin compared to in the Gln27 heterozygotes and Gln/Gln homozygotes.</p> <p>Conclusions</p> <p>In this study we were able to provide evidence on the influence of Gln27Glu genetic variant of β2AR gene on lipid phenotypes, insulin and leptin levels in the Saudi populations.</p

Optic Atrophy in a Large Specialist Hospital

"Optic atrophy is a frequent presentation in our clinics. It is not a diagnosis but represents permanent retinal ganglion cell loss that warrants investigations to establish etiology. Often the result of ischemic insult or neuritis in developed nations, we have noticed many other causes especially the effects of intracranial tumors. Our purpose was to elucidate the demographics and distribution of causes within our population.

Toll-like receptor 4 and high-mobility group box 1 are critical mediators of tissue injury and survival in a mouse model for heatstroke.

The molecular mechanisms that initiate the inflammatory response in heatstroke and their relation with tissue injury and lethality are not fully elucidated. We examined whether endogenous ligands released by damaged/stressed cells such as high-mobility group box 1 (HMGB1) signaling through Toll-like receptor 4 (TLR4) may play a pathogenic role in heatstroke. Mutant TLR4-defective (C3H/HeJ) and wild type (C3H/HeOuJ) mice were subjected to heat stress in an environmental chamber pre-warmed at 43.5 °C until their core temperature reached 42.7°C, which was taken as the onset of heatstroke. The animals were then allowed to recover passively at ambient temperature. A sham-heated group served as a control. Mutant mice displayed more histological liver damage and higher mortality compared with wild type mice (73% vs. 27%, respectively, P<0.001). Compared to wild type mice, mutant mice exhibited earlier plasma release of markers of systemic inflammation such as HMGB1 (206 ± 105 vs. 63 ± 21 ng/ml; P = 0.0018 and 209 ± 100 vs. 46 ± 32 ng/ml; P<0.0001), IL-6 (144 ± 40 vs. 46 ± 20 pg/ml; P<0.001 and 184 ± 21 vs. 84 ± 54 pg/ml; P = 0.04), and IL-1β (27 ± 4 vs. 1.7 ± 2.3 pg/ml; P<0.0001 at 1 hour). Both strains of mice displayed early release of HMGB1 into the circulation upstream of IL-1β and IL-6 responses which remained elevated up to 24 h. Specific inhibition of HMGB1 activity with DNA-binding A Box (600 µg/mouse) protected the mutant mice against the lethal effect of heat stress (60% A Box vs. 18% GST protein, P = 0.04). These findings suggest a protective role for the TLR4 in the host response to severe heat stress. They also suggest that HMGB1 is an early mediator of inflammation, tissue injury and lethality in heatstroke in the presence of defective TLR4 signaling

Bone mineral density loss in patients with cirrhosis

Background/Aims: Evidence of increased risk of osteoporosis and osteopenia in chronic liver disease and cirrhosis is inconsistent. This study aims to investigate this relationship and to identify the predictors of increased loss of bone mineral density in Saudi patients. Patients and Methods: One hundred and sixty-four patients and controls who are age and gender matched, were included in this study with 1:1 ratio. Patients' included in this study were adults with confirmed liver cirrhosis. Bone mineral densitometry (BMD) at both lumbar spine (LS) and femoral neck (FN) were collected for both groups. Univariate and multivariate regression analyses were performed to identify predictors of BMD loss. Results: Results showed that cirrhotic patients are at higher risk of developing osteoporosis or osteopenia at LS (OR 2.23, 95% CI [1.19–4.19], P = 0.01) but not at FN, when compared to control sample. Patients with cirrhosis were found to have lower vitamin D and PTH levels (P = 0.0005) and (P = 0.006), respectively. Of the possible predictors tested (gender, age, body mass index [BMI], phosphorus, calcium, parathyroid hormone (PTH), vitamin D, and Model for End Stage Liver Disease [MELD] score), female gender was the main predictor of loss of BMD at LS only (OR 4.80, 95% CI [1.47–15.73], P = 0.01). Conclusions: The study showed that cirrhotic patients are at increased susceptibility of having decreased BMD, particularly at the LS and it highlights the need for preventive measures, especially for female patients

ADRB3 polymorphism rs4994 (Trp64Arg) associates significantly with bodyweight elevation and dyslipidaemias in Saudis but not rs1801253 (Arg389Gly) polymorphism in ARDB1

Abstract Background In some populations, obesity and body weight related disorders show a correlation with polymorphisms in three subtypes of beta-adrenoceptor (β1, β2, and β3) [ADRB1, ADRB2 and ADRB3] genes. We scanned for the polymorphism of Arg389Gly (rs1801253) in ADRB1 and Trp64Arg (rs4994) in ADRB3 genes in Saudi population to determine association, if any, of these polymorphisms with obesity and related disorders. Methods We studied 329 non-related adults (33.1% men and 66.9% women), aged 18–36 years. Anthropometric measurements were recorded, and Body mass index (BMI) and waist/hip ratio were calculated; leptin, insulin, lipidogram, and glucose concentrations were determined. ADRB1 and ADRB3 polymorphisms (Arg389Gly and Trp64Arg, respectively) were screened by DNA sequencing. The subjects were divided into three groups according to BMI: normal weight (BMI < 25 kg/m2), overweight (BMI ≥25.1–29.9 kg/m2) subjects, and obese (≥30 kg/m2). Results In the age-matched groups of the normal weight, overweight and obese male and female subjects, all anthropometric parameters were found to be significantly higher, and in the obese group, all biochemical parameters were significantly elevated compared to the normal weight controls. The allelic frequency of Gly389 ADRB1 did not differ amongst the three groups, whereas the frequency of Arg64 of ADRB3 gene was significantly higher in the overweight and obese subjects, compared with the normal weight subjects. In addition, subjects carrying Arg64 allele regardless of their BMI had a greater waist and hip circumference, W/H ratio, plasma cholesterol, triglyceride, LDL, leptin, insulin, and glucose level compared to those with the wild-type Trp allele. Conclusion The results of this study have shown a significant association between the Trp64Arg polymorphism in ADRB3 gene and the development of overweight and obesity in Saudi populations. It also has an influence on the levels of lipid, insulin, leptin, and glucose, whereas, Arg389Gly polymorphism in ADRB1 is not associated with overweight, obesity or dyslipidaemias in Saudis

New-onset diabetes after kidney transplantation: Incidence, risk factors, and outcomes

Many patients develop new-onset diabetes after kidney transplantation (NODAT). Its incidence and epidemiology are unknown in the Saudi population. We aimed to study the incidence, epidemiology, and outcomes of kidney transplant recipients who developed NODAT. This is a retrospective study of all adults who received kidney transplant between January 2003 and December 2009. NODAT was defined according to the criteria outlined in the 2003 International Consensus guidelines. A total of 500 patients were included in this study, 54% were male patients. One hundred thirty-six patients (27%) developed diabetes (NODAT group). In the univariate analysis, patients were older in the NODAT group (P <0.001), were of higher weight (P = 0.006), and had positive family history of diabetes (P = 0.002). Similarly, more patients in this group had impaired glucose tolerance before transplant (P = 0.01) and history of hepatitis C infection (P = 0.005). In the multivariate analysis, older age [odds ratio (OR) 1.06], family history of diabetes (OR 1.09), hepatitis C infection (OR 1.92), and impaired fasting glucose (OR 1.79) were significant risk factors for the development of NODAT. Mortality was 6% in the NODAT group and 0.5% in the non-diabetic group had died (P <0.001). Graft survival was not different between the groups (P = 0.35). In conclusion, there is a significant risk of developing diabetes after renal transplantation. Patients are at higher risk if they are older, have a family history of diabetes, pre-transplant impaired fasting/random glucose, and hepatitis C virus infection

The Relationship between 25 (OH) D Levels (Vitamin D) and Bone Mineral Density (BMD) in a Saudi Population in a Community-Based Setting

<div><p>Background</p><p>Vitamin D deficiency has been linked to an increased risk of osteoporosis. Vitamin D deficiency has reached high levels in the Saudi population, but there is conflicting evidence both in the Saudi population, and worldwide, regarding the existence of a correlation between these low vitamin D levels and reduced BMD (bone mineral density), or osteoporosis.</p><p>Objective</p><p>The objective of this study was primarily to determine whether there was a correlation between vitamin D deficiency and osteoporosis in the Saudi population. We aimed to investigate whether the high levels of vitamin D deficiency and insufficiency would translate to higher prevalence of osteoporosis, and whether there is a correlation between vitamin D levels and bone mineral density.</p><p>Materials and methods</p><p>This was a community based cross sectional study conducted in the Family Medicine Clinics at King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia. Electronic records of 1723 patients were reviewed. Laboratory and radiology results were collected, including vitamin D levels, calcium levels, and bone mineral density scan results.</p><p>Results</p><p>Among the whole population, 61.5% had moderate to severe vitamin D deficiency with levels less than 50nmol/L. 9.1% of the population had osteoporosis, and 38.6% had osteopenia. Among the whole population, there was no significant correlation between spine or total femoral BMD and serum 25(OH) D.</p><p>Conclusion</p><p>Vitamin D deficiency is prevalent in the Saudi population. However, no correlation has been found between vitamin D deficiency and reduced bone mineral density in any age group, in males or females, Saudis or Non-Saudis, in our population in Riyadh, Saudi Arabia.</p></div