The Association Between Bone Remodeling Markers, genes polymorphisms with Incidence of Osteopenia Among Young Saudi Female.

Osteopenia and osteoporosis, are prevalent skeletal systemic conditions, cause weaker bones and an increased risk of fragility fractures. This work is aimed to evaluate the relation between bone-remolding markers and genotypes of four single nucleotide polymorphisms in young Saudi females (rs2297480 of farnesyl diphosphate synthase (FDPS), rs3736228 of Low-density lipoprotein receptor-related protein 5 (LRP5), rs1234612 of sclerostin (SOST), and rs9934438 of Vitamin K epoxide reductase complex subunit 1  (VKORC1) ). For this purpose, 750 premenopausal females aged 18 to 40 years old, either university students, postgraduates, or university employees were recruited and divided into three groups according to bone mineral density BMD (g/cm2) divided by T score into osteoporosis (n = 12), osteopenia (n = 147), and normal (n = 591). Serum SOST, BALP, calcium, phosphate, ALP, albumin, beta-CTXs and human VDR levels were determined. TaqMan SNP Genotyping assays were used to genotype four polymorphisms using real-time PCR (applied biosystem). Results showed that BALP, CTX-1 and SOST were significantly higher in the osteoporosis and osteopenia groups than in the normal group. Bone mineral density readings were considerably lower in females with the GG genotype in FDPS rs2297480 and TT genotype in LRP5 rs3736228, which increase the risk for osteopenia by 3. 6-fold and 3. 06-fold than control respectively. Also, females with the TT genotype in LRP5 rs3736228 have decreased average values for Bone Mineral Density. In conclusion, the GG genotype of FDPS rs2297480 and the TT genotype of LRP5 rs3736228 was shown to be strongly associated with osteopenia in young Saudi females with low bone mineral density and SOST levels.

Association Between Vitamin D Level and Z-Score Changes of Bone Density in College-Age Saudi Girls: A Cross-Sectional Study.

Objective: Vitamin D (VD) deficiency is a worldwide health problem. VD plays a crucial role in calcium homeostasis, phosphorus metabolism and bone health. Still much remain to understand the effect of VD deficiency on bone mass. This study aimed to evaluate the relationship between VD levels and bone mass density (BMD) among college-age Saudi females. Methods: In a cross-sectional study, 460 females with a median age of 21 years, were enrolled, completed a comprehensive, structured questionnaire which was validated by experienced endocrinologist, a dietician, and a statistician. Body mass indexes (BMI) were calculated, and BMD was estimated through quantitative ultrasound to ankle. Serum VD, calcium, phosphate, parathyroid hormone, and alkaline phosphatase were measured using chemiluminescent immunoassay technique. Results: VD deficiency reached up to 83.3% (66.9% insufficiency and 16.4% deficiency). Lower than normal BMD was detected in 18.3% of subjects, with only 1.1% having a non-age-matched high risk for osteoporosis. The significant independent predictors of Z-score were age of menarche, menstrual irregularities, dairy products consumption, physical activity, BMI, alkaline phosphatase, and history of previous VD supplementation. Conclusion: VD deficiency and low BMD are highly prevalent among college-age Saudi females. Low BMD is not linked to serum level of VD but to its previous use as a supplementation. Early lifestyle changes, attention to gynecological problems, and prevention of VD deficiency are all needed to support BMD among these girls.

Expression of toll-like receptor 4 and its connection with type 2 diabetes mellitus.

Toll-like receptor 4 (TLR4) plays an important role in modulating innate immunity. Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by impaired insulin resistance and abnormal immune response. Genetic background and consequently genetic factors might have a key role in both onset and progression of T2DM-related complications.  The aim of this work was to study the role of toll-like receptor 4 (TLR4) in the development of type 2 diabetes mellitus (T2DM). This study was carried out on 90 subjects, 30 type 2 diabetic patients, 30 patients with impaired glucose tolerance and 30 age and gender matched healthy controls. mRNA expression of (TLR4) was assessed by reverse transcriptase PCR (RT-PCR) using real time PCR.. Results showed significant statistical difference between the three studied groups  regarding BMI, serum FBG, HDL, TGs, TC, LDL, HOMA -IR and mRNA expression of TLR4 with highest level of TLR4 mRNA expression in T2DM patients. From this study, it might be concluded that high expression of (TLR4) is associated with T2DM.

Obesity and its Association with Irisin Level Among Individuals with FNDC5/Irisin Gene Variants RS16835198 and RS726344.

BACKGROUND: Irisin; a novel myokine/adipokine; encoded by FNDC5 gene have been suggested to play an important role in energy metabolism and obesity. However, the genetic variations at this locus and their effects on different metabolic parameters is still poorly understood. AIM: This study aimed to investigate the role of FNDC5/irisin gene polymorphisms (RS16835198 and RS726344) in obese individuals and their genotype phenotype correlation with circulating serum irisin level and other biochemical parameters like glucose, lipid metabolism and liver enzymes. METHODS: The study included 200 subjects divided into two groups: obese group (110 subject) and control non obese group (90 subject). All selected individuals were subjected to a comprehensive questionnaire, clinical assessment and laboratory investigations including fasting blood glucose (FBS), serum insulin, lipid profile (Total Cholesterol (TC), Triglycerides (TG), Low Density Lipoprotein (LDLc), High Density Lipoprotein (HDLc), liver enzymes (ALT, AST, GGT), Serum irisin level and HOMA-IR was calculated. DNA extraction and FNDC5 allelic discrimination analysis for FNDC5 SNPs, rs16835198and rs726344 using the TaqMan SNP genotyping assays by Real time PCR. RESULTS: In obese group; serum irisin was significantly lower (0.55 ± 0.2) than control group (1.7 ± 0.3) P value < 0.001. Regarding genotype and allele frequency, T allele of rs16835198 polymorphism is associated with high BMI, high total cholesterol, TG and LDL-C, low level of serum HDL-C, high FBS, low serum insulin, low HOMA-IR and low serum level of irisin. While G allele of rs726344 is significantly associated with high BMI, FBS, low serum insulin and HOMA-IR, High total cholesterol, TG, LDL-C, low level of HDL-C and low serum irisin. CONCLUSION: Our data suggest that FNDC5 SNPs, rs16835198and rs726344 are associated with obesity in Egyptian population. GG genotype and G allele of rs726344 variant and TT genotype and T allele of rs16835198 variant may increase the susceptibility to obesity and there were a genotype phenotype correlation with circulating serum irisin and several metabolic parameters.

Leptin receptor gene (A/G) polymorphism rs1137101 and renal cell carcinoma.

Leptin plays an important role in carcinogenesis as leptin/leptin receptor signaling promotes the angiogenesis, proliferation, and inhibits epithelial cell apoptosis. Variants in the leptin receptor gene have potential associations with renal cell carcinoma (RCC). We aimed to investigate association of rs1137101 (A/G) polymorphism at LEPR gene with risk of RCC and patients survival. 123 individuals were classified into group I: 73 RCC patients and group II: 50 healthy controls. Genotyping of the Gln223Arg (A/G) polymorphism rs1137101 at LEPR gene was analyzed using allelic discrimination assay by Real-Time PCR technique. GG genotype was the most frequent among RCC patients (67.1%), while AA genotype was the most frequent in controls (60%); (p < 0.001). By univariate cox regression: gene polymorphism (GG versus GA +AA), stage, histopathologic subtype, and grade were found to affect survival significantly; however, the multivariate analysis showed that only gene polymorphism (GG versus GA +AA) and tumor stage significantly affect survival. LEPR gene variants rs1137101 might be a candidate risk factor for RCC in Egypt. GG genotype is associated with more aggressive tumor behavior and shorter survival compared with GA & AA genotypes so, genotyping of Gln223Arg (A/G) rs1137101 could also predict RCC outcome.

Correlation between serum leptin and its gene expression to the anthropometric measures in overweight and obese children.

Obesity is a multifactor disorder with evidence supporting the role of the genetic factor in its etiology. The present study evaluates the relationship between leptin G2548A (rs7799039) and leptin receptors (Gln223Arg (rs1137101) genotyping and its leptin level and the risk of childhood obesity. This case-control study was conducted on 168 overweight and obese Saudi children and 126 non obese one served as control. Fasting insulin, leptin, blood glucose, lipid profile levels were measured. HOMA- IR, and BMI were assessed. Genotyping of leptin and leptin receptor gene variants was done by SNP real-time PCR method. GG genotype and G allele of rs1137101 were significantly higher in overweight and obese children than controls. It showed significant association with risk of obesity OR 7.1 [ 95% CI: 3.4 - 14.8] and OR 2.8 [ 95% CI: 2.0 - 4.1] respectively. Leptin level was significantly greater in patients than controls (p<0.000*) with GG and AG genotypes having the highest level of leptin when compared with another genotype in the obese group. As regards, rs7799039 AA genotype showed significant higher leptin level than other genotypes in the same group with a non-significant difference in genotypes distribution between obese and controls. rs1137101 variant of leptin receptor and fasting leptin level are correlated with overweight and obesity in Saudi children. The GG genotype of leptin receptors rs1137101 and higher serum leptin levels can be used as risk factors for childhood obesity.

Transforming Growth Factor-ß1 gene polymorphism and osteoporosis in postmenopausal egyptian women.

Transforming growth factor-ß1 (TGF-ß1) is a wide spread bone matrix protein that affect the function, formation and cell-cell interactions of osteoclasts and osteoblasts to regulate bone remodeling and sustain adequate bone mass. The aim of this study is to evaluate the role of the two polymorphism of transforming growth factor-ß1 T869C and C-509T in developing osteoporosis in postmenopausal Egyptian women. This study was performed on 138 postmenopausal osteoporosis/osteopenic women and 128 postmenopausal female control group. There was a significant statistical difference in the CC, CT and TT (T869C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value <0.001). There was a non-significant statistical difference in the CC, CT and TT (T-509C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value <0.082). There was a significant statistical difference between TT,CT and CC of (T869C) and T score, Z score and calcium of osteopenia/osteoporosis group (p value <0.001). There was a non-significant statistical difference between TT, CT and CC of (T-509C) and T score, Z score of osteopenia/osteoporosis group (p value 0.32,0.31),but there was a statistically significant difference between the three genotyping and serum calcium and creatinine (p value 0.04). Multivariate regression analysis showed that T869C polymorphism is a significant risk factor for osteopenia/ osteoporosis (OR 3.57, 95% CI= 1.56-5.67). We concluded that T869C polymorphism of the TGF-ß1 gene has an impact on bone mineral density and enhancement of the susceptibility to osteopenia/osteoporosis in Egyptian women.

Serum amyloid a gene polymorphism and its association with lipid profile in Saudi females with osteoporosis.

BACKGROUND AND OBJECTIVE: Osteoporosis can be defined as a systemic skeletal disease characterized by low bone mass and micro architectural decline of bone tissue. Serum amyloid A (SAA) is a family of protein that increases up to 1,000-fold in blood during inflammation. In this study, we aimed to study the relationship between SAA1 gene polymorphism (rs12218) and lipid profile and osteoporosis. METHODS: The study was performed on the female students of Taibah University in Al Medina, KSA during June 2014 to April 2015. According to BMD; osteoporosis group (138 students) and control group (128 students). All groups were subjected to; BMI, BMD, calcium, phosphorus, creatinine, lipid profile and SAA. Polymerase chain reaction and Real Time were done to determine the distribution of allele and genotype frequency of SAA (rs12218) C/T polymorphism. RESULTS: This study shows that the TT genotype of rs12218 was more frequent in osteoporosis group than control group (P<0.001). Also, TT genotype and T allel was found to be associated with plasma total cholesterol, TG, LDLc, HDLc, Tscore, Zscore and SAA1 level in osteoporosis group (P=0.000, P=0.05, and P=0.000, P=0.000, P=0.01, P=0.02, P=0.000 respectively). The logistic regression analysis with and without lipid disorders in the osteoporosis group also show that the TT genotype of rs12218 still differed significantly between these two groups (P=0.001, OR=1.814, 95% CI: 0.719-4.577). CONCLUSION: The results of this study shows a significant association between TT genotype of rs12218 and both lipid level and osteoporosis in Saudi female population.