Association of Alzheimer's Disease with Genetic Variants of Apolipoprotein E, Clusterin, TNF-α, and IL-6 Among Elderly Saudis.

BACKGROUND: In the wake of the warning by WHO that the prevalence of dementia may have a rise of 125% in the Middle East by 2050, identification of the genetic risk factors in Arab populations is urgent. OBJECTIVES: To investigate the association of Single Nucleotide Polymorphisms (SNPs) in apolipoprotein E (ApoE), clusterin (CLU), tumor necrotic factor- α (TNF-α) and interleukin-6 (IL-6) genes, with risk of Alzheimer's disease (AD) in Saudi Arabian participants. METHODS: A total of 42 Saudi AD patients and 23 age-matched control participants were genotyped for eight SNPs: rs429358, rs7412 (ApoE); rs11136000, rs1532278 (CLU); rs1800629, rs1799724 (TNF-α) and rs1800796, rs1800795(IL-6), by RT-PCR using the TaqMan assay. Serum concentrations of amyloid beta peptide 1-40(Aß1-40), amyloid beta peptide 1-42(Aß1- 42), CLU and some other biochemical markers were measured. RESULTS: A significant increase (p=0.004) in the serum CLU level was detected in the AD group (340.4 ± 74.6) compared with control group (265.0 ± 80.9). For rs1532278 (CLU), genotype GA was significantly higher in AD patients (57.1%) than in the control participants (26.1%), [p=0.024, OR = 4.00, 95% CI (1.20-13.28)]. For the ApoE SNP rs7412, 40.4% of patients carried a TT genotype, whereas it was completely absent in the controls [p = 0.020, OR = 30.53, 95% CI (1.73 - 540.05)].For rs429358 (ApoE), patients showed a significantly increased frequency of the TC genotype [p = 0.006, OR = 9.33, 95% CI (1.89-46.19)] and TT [p = 0.045, OR = 19.76, 95% CI (1.07-366.0)] genotype than controls. AD patients with CC genotype for ApoE rs429358 had significantly lower levels of Aß1-40 (p=0.04) in AD patients than controls. Carriers of genotype GG for rs1800629 (TNF-α) showed significantly higher levels of serum IL-6 (p = 0.04) in AD patients. CONCLUSION: Genetic variants in ApoE and CLU may influence susceptibility to AD among Saudi Arabian participants.

Difference on the prevalence, patterns and awareness of soft drink consumption among male and female Arab students.

BACKGROUND: The increase in soft drink (SD) consumption is emerging as a serious health issue. Our aim is to explore the prevalence and awareness regarding SD consumption among Saudi students. METHODS: This cross-sectional study included 1000 apparently healthy Saudi students (527 males, 473 females) aged 16-23 years. A designed questionnaire including various sections was used to obtain the required information. RESULTS: The BMI and frequency of SD consumption were significantly higher in males (P < 0.001) than females, whereas, females exhibited higher awareness and knowledge regarding SD consumption than males. The SD consumption in females was due to society, taste, availability and markets, whereas in males it was due to cheap price. Females support the implementation of new policies to prevent consumption of SD. CONCLUSIONS: Arab students exhibited a high prevalence of SD consumption especially in males. Although females showed more awareness and knowledge about SD, various misconceptions were notable in both sexes. New policies, health promotion campaigns must be organized to raise awareness among children and parents. Parents and health educators should motivate and encourage the children to consume more water in the context of a healthy balanced diet.

PTHR1 Genetic Polymorphisms Are Associated with Osteoporosis among Postmenopausal Arab Women.

The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1-L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO (OR = 1.49, 95% CI 1.0-2.1, P = 0.03). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; P = 0.048]. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO.

High glucose load and endotoxemia among overweight and obese Arab women with and without diabetes: An observational study.

Dietary intake influences gut microbiota activity. Nevertheless, there is a lack of evidence available that illustrates the acute effects of high glucose meal on metabolic endotoxemia. The present study assessed the acute impact of high glucose meal on endotoxemia and other clinical parameters in Saudi females with varying degrees of glycemia.The subjects were 64 consenting pre-menopausal women, grouped into 3: control [n = 14 lean, non-T2DM, BMI = 22.2 ±â€Š2.2 kg/m]; overweight [n = 16, non-T2DM, BMI = 28.5 ±â€Š1.5 kg/m] and T2DM [n = 34, BMI = 35.2 ±â€Š7.7 kg/m]. After an overnight fast, all subjects were given a standardized high-glucose (75 g) meal. Anthropometrics were taken and blood samples were withdrawn at baseline and postprandial (0, 2 and 4-hours), serum glucose, endotoxin and lipid profile were quantified.At baseline, total cholesterol, LDL-cholesterol, triglycerides and serum glucose levels were significantly higher (P values <.01) whereas significantly lower HDL-cholesterol levels (P < .01) were observed in T2DM subjects compared to other groups. Baseline endotoxin levels were highest in the overweight group (3.2 ±â€Š1.1 mmol/L) as compared to control (2.0 ±â€Š0.5 mmol/L) and T2DM (2.7 ±â€Š1.2 mmol/L) (P = .046). HDL-cholesterol, LDL-cholesterol and triglycerides, significantly decreased in the T2DM group after 2 hours (P values <.05), whereas unremarkable changes observed in other groups. Lastly, endotoxin levels significantly increased only in the overweight group (3.2 ±â€Š1.1 vs 4.2 ±â€Š1.4 mmol/L; P < .05), 4 hours postprandial.High glucose meal elevates endotoxemia only among overweight subjects and impairs dysbiosis.

Vitamin D Supplementation Is Associated with Increased Glutathione Peroxidase-1 Levels in Arab Adults with Prediabetes.

Vitamin D supplementation may be used to lower oxidative stress. This interventional study aimed to investigate the effects of vitamin D supplementation on glutathione peroxidase 1 (GPx1) levels and other parameters in Arab adults with prediabetes. A total of 203 Saudi adults with prediabetes and vitamin D deficiency [intervention group, N = 146 (53 males and 93 females); control group, N = 57 (25 males and 32 females)] were included in this non-randomized, six-month intervention study. The intervention group received 50,000 international units (IU) cholecalciferol tablets once a week for two months, then twice a month for the next two months, followed by 1000 IU daily for the last two months. The control group received no supplementation. Serum 25(OH)D, lipid profile, glucose, C-reactive protein (CRP) and GPx1 were measured at baseline and after six months. Post-intervention, GPx1 concentrations increased significantly in the intervention group [17.3 (11.5-59.0) vs 26.7 (11.4-59.9) p < 0.01] while no changes were observed in the control group (p = 0.15). This significant increase in 25(OH)D and GPx1 levels persisted after adjusting for age and BMI. Stratification according to sex revealed that this favourable increase in GPx1 was true only for males (p = 0.002). In all groups, baseline GPx1 was inversely correlated with low density lipoprotein (LDL)-cholesterol (r = -0.26, p < 0.01) and body mass index (BMI) (r = -0.20, p < 0.05), while positively correlated with age (r = 0.18, p < 0.05) and systolic blood pressure (r = 0.19, p < 0.05). In conclusion, vitamin D supplementation favourably enhanced GPx1 levels in adult Arabs with prediabetes, particularly in males.

Influence of bone mineral density in circulating adipokines among postmenopausal Arab women.

Osteoporosis and osteopenia has a significant link with substantial fracture risk. Epidemiological data revealed a protective role of adipose tissue on bone biology in postmenopausal osteoporosis. The current study assessed the associations between select adipokines and bone mineral density (BMD) in postmenopausal women. A total of 175 Saudi postmenopausal women were selected and categorized based on their BMD (normal & low-BMD). Circulating levels of select adipokines (adiponectin, resistin, leptin, and adipsin), insulin, 25(OH)D and RANKl were determined using commercially available assay kits. BMD was measured by dual-energy X-ray absorptiometry (DXA). Overall and among low-BMD subjects, adiponectin consistently showed a significant inverse association with BMD (overall -0.34, p < 0.01; low BMD group -0.34, p < 0.01). In multiple regression, adiponectin (-0.29 ±â€¯0.06, p < 0.00) and resistin (-0.08 ±â€¯0.04, p < 0.05) were inversely significant with BMD overall, but after stratification the significance was lost for resistin (-0.05 ±â€¯0.04, p < 0.224) whereas adiponectin remained (-0.22 ±â€¯0.07, p < 0.02) in low-BMD subjects. Adipsin, leptin and lipocalin-2 showed no significant associations. Findings of the present study revealed that only adiponectin showed a significantly strong inverse association with low BMD, suggesting that insulin sensitivity may influence bone health in Arab postmenopausal women.

Favorable Changes in Fasting Glucose in a 6-month Self-Monitored Lifestyle Modification Programme Inversely Affects Spexin Levels in Females with Prediabetes.

Spexin (SPX) is a novel peptide thought to have a role in various metabolic regulations. Given its presumed body-weight regulatory functions, we aimed to determine whether lifestyle intervention programs on weight loss and fasting glucose (FG) improvement among people with impaired glucose regulation also alter levels of circulating SPX. A total of 160 Saudi adult males and females with prediabetes were randomly selected from a larger cohort (N = 294) who underwent a 6-month lifestyle modification program to improve their glycemic status. Participants were split into two groups based on differences in glucose levels post-intervention, with the first 50% (improved group) having the most significant reduction in FG. SPX was measured at baseline and after 6 months. Changes in SPX was significant only in the improved group [baseline: median (Q1-Q3) of 164 pg/ml (136-227) vs follow-up: 176 pg/ml (146-285); p < 0.01]. When stratified by sex, the significant increase was observed only in females [159 pg/ml (127-252) vs 182.5 (152,369.1); p < 0.01]. Furthermore, SPX levels showed a significant inverse association with FG (ß = -0.22, p = 0.003) even after adjustment with age and BMI, again only in females. Circulating SPX levels increase over time in people with prediabetes, particularly women who responded favorably in a 6-month lifestyle intervention program. Whether an unknown mechanism regulating the sexual disparity seen in SPX levels post-intervention exists should be further investigated using a larger sample size.

Metabolic Syndrome in Arab Adults with Low Bone Mineral Density.

There are discrepancies in the reports on the association of metabolic syndrome (MetS) and its components with bone mineral density (BMD) and hence more population-based studies on this subject are needed. In this context, this observational study was aimed to investigate the association between T-scores of BMD at lumbar L1-L4 and full MetS and its individual components. A total of 1587 participants (84.7% females), >35 years and with risk factors associated with bone loss were recruited from February 2013 to August 2016. BMD was done at L1-L4 using dual-energy X-ray absorptiometry (DXA). T-Scores were calculated. Fasting blood samples and anthropometrics were done at recruitment. Fasting lipid profile and glucose were measured. Screening for full MetS and its components was done according to the National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) criteria. Logistic regression analysis revealed that the odds of having full MetS increased significantly from the lowest T-score tertile to the highest one in both sexes (OR, odd ratio (95% CI, confidence interval) of tertile 2 and 3 at 1.49 (0.8 to 2.8) and 2.46 (1.3 to 4.7), p = 0.02 in males and 1.35 (1.0 to 1.7) and 1.45 (1.1 to1.9), p < 0.01 in females). The odds remained significant even after adjustments with age, body mass index (BMI), and other risk factors associated with bone loss. Among the components of MetS, only central obesity showed a significant positive association with T-score. The study suggests a significant positive association of T-score (spine) with full MetS irrespective of sex, and among the components of MetS this positive association was seen specifically with central obesity.

Efficacy of vitamin D supplementation according to vitamin D-binding protein polymorphisms.

OBJECTIVES: The aim of this study was to determine the influence of vitamin D-binding protein (DBP) gene polymorphisms in vitamin D metabolites before and after vitamin D supplementation. METHODS: In all, 234 participants (126 women; 108 men) with vitamin D deficiency [25(OH)D <50 nmol/L] were given 50 000 IU of vitamin D supplements for 8 wk followed by daily maintenance of 1000 IU for 4 mo. Two single-nucleotide polymorphisms (rs4588 and rs7041) in DBP coding gene were assessed. RESULTS: Baseline 25(OH)D was significantly in higher in participants with homozygous major genotype of rs7041 than other genotypes (P = 0.02). Postsupplementation 25(OH)D was significantly higher in participants with homozygous major genotypes of either rs4588 and rs7041 than other genotypes (P < 0.001). Participants with the minor allele of either rs4588 or rs7041 were 2.9 (1.9-4.5) times and 3.7 (2.1-6.6) times, respectively, more likely to be non-responders (postsupplementation 25 OHD <50 nmol/L) than those homozygous for the major allele at these locations (P < 0.001). Furthermore, participants with homozygous minor and heterozygous genotype of rs7041 were 6.2 and 4.2times more likely to be non-responders than those with the homozygous major genotype (P < 0.001) even after adjustments for age, sex, body mass index, baseline 25(OH)D concentration, and other alleles. Participants with homozygous minor and heterozygous genotypes of rs4588 were 4.1 and 12.4times more likely to be non-responders than those with homozygous major genotypes. These significant risks, however, were lost after adjustment. CONCLUSIONS: rs7041 and rs4588 variants of the DBP gene are associated with variations in 25(OH)D levels and efficacy of response to vitamin D supplementation in Saudi Arabian adults.

Efficacy of different modes of vitamin D supplementation strategies in Saudi adolescents.

Vitamin D deficiency is rampant in the Middle East, even in children and adolescents. This study was designed to investigate the effects of different vitamin D repletion strategies commonly used on serum vitamin D levels of Saudi adolescents. STUDY DESIGN: A 6-month multi-center, controlled, clinical study, involving 34 schools in the central region of Riyadh, Saudi Arabia. Different strategies of vitamin D supplementation were tested (200 ml fortified milk of different brands or vitamin D tablet (1,000IU). Anthropometrics were taken and fasting blood samples withdrawn at baseline and after intervention for the quantification of serum glucose, lipid profile and 25(OH) vitamin D. A significant increase in 25(OH)D level was observed in subjects supplemented with vitamin D tablet, milk brand 2 and milk brand 4, whereas subjects supplied with fortified milk brands 1 and 3 respectively, exhibited a significant decrease in 25(OH)D levels. Analysis of covariance showed that after adjusting for baseline 25(OH)D, age, gender and BMI, the mean 25(OH)D levels of children who were taking vitamin D tablet (9.1 ±â€¯0.8 nmol/l) and milk brand 4 were significantly higher (7.3 ±â€¯1.1 nmol/l) than children taking milk brand 2 (1.6 ±â€¯1.0 nmol/l). Subjects supplied with milk brands 1 and 2 exhibited a significant increase in total cholesterol level, while it dropped significantly in subjects taking milk brand 3, while no changes were observed in other groups. Different strategies in vitamin D supplementation used in this clinical study elicited varying degrees of improvement in serum 25(OH)D level. The observed outcomes were dependent on the strategy and gender in the Saudi adolescent population, with oral tablet supplementation being favored in boys.

Sex-specific expression of apolipoprotein levels following replenishment of vitamin D.

Numerous studies have been done to establish the relationship between vitamin D and lipids, yet a definitive causal link is not found. This interventional study aims to evaluate and compare levels of apolipoproteins among vitamin D deficient subjects at baseline and after they achieved full vitamin D status correction.120 Saudi adults with vitamin D deficiency [25(OH)D < 50nmol/l] were recruited and given 50,000IU cholecalciferol weekly for first 2 months, then twice a month for next 2 months, followed by daily 1000IU until month 6. Blood samples were taken at baseline and after 6 months. Serum 25(OH)D, lipid profile and apolipoproteins (A1, A2, B, C1, C2, C3, E and H) were analyzed using commercially available kits. Overall, serum 25(OH)D increased significantly(63.3 ±â€¯16.5nmol/l at end of study vs. 32.5 ±â€¯10.8 at baseline; p < 0.0001). In parallel, a significant increase in apolipoproteins C1, C2, C3 and E (all p-values < 0.01) and a significant decrease in apolipoprotein B (p = 0.02) was observed. Following, stratification according to sex, apolipoproteins C2 and C3 significantly increased only in males (p-values < 0.01) while apolipoprotein C1 significantly increased only in females (p < 0.01). In addition, apolipoprotein B significantly decreased only in females (p = 0.002). These results suggests role of vitamin D in modulation of circulating levels of lipoproteins. The sexual dimorphism observed in circulating levels of measured apolipoproteins following vitamin D correction may explain, in part, known sexual disparity in the events of cardiometabolic health.

Vitamin D Receptor Gene Polymorphisms Modify Cardiometabolic Response to Vitamin D Supplementation in T2DM Patients.

There is conflicting evidence on the favorable effects of vitamin D supplementation on metabolic profile in Type 2 diabetes mellitus (T2DM) patients and this might be due to genetic variations in vitamin D receptors (VDRs). Thus, we studied the metabolic effects of a 12-month vitamin D supplementation in T2DM patients according to VDR polymorphisms. A total of 204 T2DM subjects received 2000 IU vitamin D3 daily for 12 months. Serum 25(OH)D and metabolic profiles were measured at baseline and after 12 months. VDR polymorphisms (Taq-I, Bsm-I, Apa-I and Fok-I) were identified using TaqMan genotyping assays. Vitamin D supplementation significantly increased HOMA ß-cell function (p = 0.003) as well as significantly decreased triglycerides, total and LDL-cholesterol (p < 0.001). The lowest increment in 25(OH)D levels was detected in patients with Fok-I CC genotypes (p < 0.0001). With vitamin D supplementation, Taq-I GG genotype carriers showed significant improvements in triglycerides, LDL- and total cholesterol, insulin, HbA1c and HOMA-IR (p < 0.005, 0.01, < 0.001, < 0.005, 0.03 and 0.01, respectively). Similarly, Bsm-I TT genotype carriers showed significant improvements in triglycerides (p = 0.01), insulin and HOMA-IR (p-values < 0.05). In conclusion, improvements in metabolic profile due to vitamin D supplementation is influenced by VDR polymorphisms, specifically for carriers of Taq-I GG and Bsm-I TT genotypes.

Circulating betatrophin in healthy control and type 2 diabetic subjects and its association with metabolic parameters.

AIMS: Betatrophin, a newly identified liver and adipose tissue-derived hormone, has been suggested as an inducer of ß-cell proliferation in mice. However, the physiological role of betatrophin remains poorly understood in humans. Hence, the aim of this study was to investigate circulating betatrophin concentrations in normal and type 2 diabetes mellitus (T2DM) Saudi subjects and its association with various metabolic parameters. METHODS: In this cross-sectional study, 200 Saudi adults (81 healthy non-T2DM controls, age: 41.43±8.35 [mean±SD]; BMI: 31.58±5.49 and 119 T2DM subjects, age: 48.78±11.76years; BMI: 30.25±4.83kg/m(2)) were studied. Anthropometric and fasting serum biochemical data were collected. Circulating betatrophin was measured using an enzyme-linked immunosorbent assay (ELISA) based kit. RESULTS: We observed significantly higher levels of betatrophin in T2DM subjects compared to healthy controls (882.19±329.06 vs 657.14±261.04pg/ml, p<0.001). Furthermore, in T2DM subjects, betatrophin level was positively associated with blood pressure and serum fasting glucose (p<0.05). CONCLUSIONS: Our results suggest that circulating betatrophin is significantly elevated in subjects with T2DM compared to healthy controls. Increase in the level of betatrophin in T2DM subjects might be a compensatory mechanism for enhanced insulin demand in T2DM condition.

Association of VDR-gene variants with factors related to the metabolic syndrome, type 2 diabetes and vitamin D deficiency.

The prevalence of metabolic syndrome (MetS) is rising alarmingly in the Saudi Arabian population. This study was conducted to assess the association between vitamin D receptor (VDR) polymorphisms and genetic susceptibility to components of the metabolic syndrome, type 2 diabetes mellitus (T2DM), and vitamin D deficiency in the Saudi Arabian population. Five-hundred-seventy Saudi individuals (285 MetS and 285 controls) were enrolled in this cross-sectional study. TaqI, BsmI, ApaI and FokI single nucleotide polymorphisms (SNPs) of the VDR gene were genotyped. The CT genotype and allele T of BsmI were associated with lower HDL-C levels [OR 0.60 (0.37, 0.96), p=0.03] and obesity [OR 1.4 (1.0, 1.90), p=0.04], respectively. The CT genotype and the dominant model CT+TT of BsmI were associated with increased risk of diabetes [OR 1.7 (1.2, 2.4), p=0.007], and [OR 1.5 (1.1, 2.2), p=0.01], respectively. On the contrary, the CT and CT+CC genotypes of FokI exhibited an association with a reduced risk of diabetes [OR 0.70 (0.49, 0.99), p=0.05] and [OR 0.67 (0.48, 0.94), p=0.02], respectively. The allele C of FokI was associated with lower risk of developing T2DM [OR 0.73 (0.56, 0.95), p=0.02]. The prevalence of vitamin D deficiency was lower in subjects with the AC genotype of ApaI [OR, 0.34 (0.14, 0.80), p=0.01]. Components of the MetS such as obesity, low HDL and T2DM were associated with the VDR gene. FokI and BsmI have protective and facilitative effects on the risk for T2DM, while the ApaI genotype was associated with reduced vitamin D deficiency.

ABCA1 C69T gene polymorphism and risk of type 2 diabetes mellitus in a Saudi population.

Type 2 diabetes mellitus (T2DM) is a disease induced by complex interactions between environmental factors and certain genetic factors. Genetic variants in the Adenosine Binding Cassette Transporter Proteins 1 (ABCA1) have been associated with abnormalities of serum lipid levels of high-density lipoprotein (HDL-C). Decreased serum levels of HDL-C have often been observed in T2DM cases, and this condition has been considered to be involved in the mechanism of insulin resistance (IR). Therefore, we investigated possible association between ABCA1 C69T gene polymorphism and T2DMin a Saudi population. This study was carried out with 380 healthy control subjects and 376 T2DM patients. Genotyping of ABCA1 C69T polymorphism was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique. We observed that the frequency of the T allele of the ABCA1 C69T gene was significantly higher in healthy subjects compared to T2DMpatients (0.28 vs 0.45; p less than 0.0001; OR (95 percent CI) = 0.4624 (0.3732-0.5729), and therefore the T allele may be a protective factor against T2DM in the Saudi population.