SNP rs498055 in the predicted gene LOC439999 on chromosome 10 was recently identified as being strongly associated with late-onset Alzheimer disease (LOAD). This SNP falls within a chromosomal region that has engendered continued interest generated from both preliminary genetic linkage and candidate gene studies. To independently evaluate this interesting candidate SNP we examined four independent datasets, three family-based and one case-control. All the cases were late-onset AD Caucasian patients with minimum age at onset ≥ 60 years. None of the three family samples or the combined family-based dataset showed association in either allelic or genotypic family-based association tests at p < 0.05. Both original and OSA two-point LOD scores were calculated. However, there was no evidence indicating linkage no matter what covariates were applied (the highest LOD score was 0.82). The case-control dataset did not demonstrate any association between this SNP and AD (all p-values > 0.52). Our results do not confirm the previous association, but are consistent with a more recent negative association result that used family-based association tests to examine the effect of this SNP in two family datasets. Thus we conclude that rs498055 is not associated with an increased risk of LOAD. 相似文献
The role of ADIPOQ gene variants on metabolic improvements after weight change secondary to different hypocaloric diets remained unclear. We evaluate the effect of rs3774261 of ADIPOQ gene polymorphism on biochemical improvements and weight change after high polyunsaturated fat hypocaloric diet with a Mediterranean dietary pattern for 12 weeks. A population of 361 obese subjects was enrolled in an intervention trial with a calorie restriction of 500 calories over the usual intake and 45.7% of carbohydrates, 34.4% of fats, and 19.9% of proteins. The percentages of different fats was; 21.8% of monounsaturated fats, 55.5% of saturated fats, and 22.7% of polyunsaturated fats. Before and after intervention, an anthropometric study, an evaluation of nutritional intake and a biochemical evaluation were realized. All patients lost weight regardless of genotype and diet used. After 12 weeks with a similar improvement in weight loss (AA vs. AG vs. GG); total cholesterol (delta: −28.1 ± 2.1 mg/dL vs. −14.2 ± 4.1 mg/dL vs. −11.0 ± 3.9 mg/dL; p = 0.02), LDL cholesterol (delta: −17.1 ± 2.1 mg/dL vs. −6.1 ± 1.9 mg/dL vs. −6.0 ± 2.3 mg/dL; p = 0.01), triglyceride levels (delta: −35.0 ± 3.6 mg/dL vs. 10.1 ± 3.2 mg/dL vs. −9.7 ± 3.1 mg/dL; p = 0.02), C reactive protein (CRP) (delta: −2.3 ± 0.1 mg/dL vs. −0.2 ± 0.1 mg/dL vs. −0.2 ± 0.1 mg/dL; p = 0.02), serum adiponectin (delta: 11.6 ± 2.9 ng/dL vs. 2.1 ± 1.3 ng/dL vs. 3.3 ± 1.1 ng/dL; p = 0.02) and adiponectin/leptin ratio (delta: 1.5 ± 0.1 ng/dL vs. 0.3 ± 0.2 ng/dL vs. 0.4 ± 0.3 ng/dL; p = 0.03), improved only in AA group. AA genotype of ADIPOQ variant (rs3774261) is related with a significant increase in serum levels of adiponectin and ratio adiponectin/leptin and decrease on lipid profile and C-reactive protein (CRP). 相似文献
BackgroundBariatric surgery is currently the most effective long-term treatment for severe obesity. However, interindividual variation in surgery outcome has been observed, and research suggests a moderating effect of several factors including baseline co-morbidities (e.g., type 2 diabetes [T2D] and genetic factors). No data are currently available on the interaction between T2D and variants in brain derived neurotrophic factor (BDNF) and its effect on weight loss after surgery.ObjectivesTo examine the role of the BDNF Val66Met polymorphism (rs6265) and the influence of T2D and their interaction on weight loss after bariatric surgery in a cohort of patients with severe obesity.SettingUniversity hospital in Spain.MethodsThe present study evaluated a cohort of 158 patients with obesity submitted to bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for 24 months (loss to follow-up: 0%). During the postoperative period, percentage of excess body mass index loss (%EBMIL), percentage of excess weight loss (%EWL), and total weight loss (%TWL) were evaluated.ResultsLongitudinal analyses showed a suggestive effect of BDNF genotype on the %EWL (P = .056) and indicated that individuals carrying the methionine (Met) allele may experience a better outcome after bariatric surgery than those with the valine/valine (Val/Val) genotype. We found a negative effect of a T2D diagnosis at baseline on %EBMIL (P = .004). Additionally, we found an interaction between BDNF genotype and T2D on %EWL and %EBMIL (P = .027 and P = .0004, respectively), whereby individuals with the Met allele without T2D displayed a greater %EWL and greater %EBMIL at 12 months and 24 months than their counterparts with T2D or patients with the Val/Val genotype with or without T2D.ConclusionOur data showed an association between the Met variant and greater weight loss after bariatric surgery in patients without T2D. The presence of T2D seems to counteract this positive effect. 相似文献
Background: A recent genome-wide association study has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population.
Methods: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS. Interaction analysis was examined by SNPStats web tool.
Results: After adjusting for gender, age, body mass index (BMI), hypertension, diabetes and smoking, compared with CC genotype, we observed that GC and GG/GC genotypes were associated with a significantly decreased risk of AS (OR?=?0.76, 95% CI?=?0.58–0.99 and OR?=?0.76, 95% CI?=?0.58–0.98, respectively). The decreased risk was more obvious among subgroups with high BMI (OR?=?0.63, 95% CI?=?0.45–0.88), no hypertension (OR?=?0.66, 95% CI?=?0.46–0.94), diabetes (OR?=?0.33, 95% CI?=?0.17–0.64), and smoking (OR?=?0.65, 95% CI?=?0.44–0.95) in the dominant model (GG/GC vs CC). Interaction analysis also revealed that compared with non-diabetic patients with CC genotype, diabetic patients with CC genotype had a 4.48-fold (OR?=?4.48; 95% CI?=?2.98–6.72) increased risk of AS.
Conclusion: Our data suggested that GC and GG/GC of rs4376531 contributed to a decreased risk of AS while CC genotype, interacting with diabetes, increased the stroke risk in Han Chinese population. 相似文献
Sleep problems increase with ageing. Increasing evidence suggests that sleep problems are not only a consequence of age‐related processes, but may independently contribute to developing vascular or neurodegenerative brain disease. Yet, it remains unclear what mechanisms underlie the impact sleep problems may have on brain health in the general middle‐aged and elderly population. Here, we studied sleep's relation to brain functioning in 621 participants (median age 62 years, 55% women) from the population‐based Rotterdam Study. We investigated cross‐sectional associations of polysomnographic and subjectively measured aspects of sleep with intrinsic neural activity measured with resting‐state functional magnetic resonance imaging on a different day. We investigated both functional connectivity between regions and brain activity (blood‐oxygen‐level‐dependent signal amplitude) within regions, hierarchically towards smaller topographical levels. We found that longer polysomnographic total sleep time is associated with lower blood‐oxygen‐level‐dependent signal amplitude in (pre)frontal regions. No objective or subjective sleep parameters were associated with functional connectivity between or within resting‐state networks. The findings may indicate a pathway through which sleep, in a ‘real‐life’ population setting, impacts brain activity or regional brain activity determines total sleep time. 相似文献