RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect metabolic changes and insulin resistance after a standard hypocaloric diet

Background

Role of BDNF variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients.

T-cell activation Rho GTPase–activating protein expression varies with inflammation location and severity in Crohn's disease

Background

The T-cell activation Rho GTPase–activating protein (TAGAP) gene has a regulatory role in T cell activation. We have previously suggested a correlation between the TAGAP-associated single nucleotide polymorphism rs212388 and protection from anal sepsis in Crohn's disease (CD) patients. The present study sought to evaluate TAGAP's expression in colonic tissue of CD patients with varying disease severity and location.

Materials and methods

Five transverse, 17 left, and five sigmoid colectomy specimens from 27 CD patients with varying disease severity (16 male, mean age at diagnosis 26.4 ± 2.2 y) were evaluated for TAGAP messenger RNA expression. Fisher exact, Mann–Whitney, and Welch two-sample t-tests were used for statistical evaluation. Immunohistochemistry confirmed results.

Results

Patients with tissue demonstrating lower TAGAP messenger RNA expression (less than the overall mean) were younger at diagnosis (mean age 21.1 ± 6.3 versus 32.5 ± 13 y, P = 0.009). Increased TAGAP expression was seen in moderate or severely diseased tissue versus tissue with no or mild disease (RQ = 1.3 ± 0.34 versus 0.53 ± 0.09, P = 0.050). This was the most dramatic in the sigmoid colon (P = 0.041). TAGAP expression was increased in more distal tissue with a significant difference seen when comparing transverse versus sigmoid colon with moderate or severe disease (0.51 ± 0.14 versus 1.9 ± 0.37, P = 0.049).

Conclusions

Colonic expression of TAGAP in CD patients varied according to disease severity and location, being the most elevated in patients with severe disease in the sigmoid colon. Whether changes in TAGAP expression are a result of disease response or inherent to the disease pathophysiology itself remains to be determined. This gene warrants further investigation for its role in CD.     

The risk of nonsyndromic cleft lip with or without cleft palate and Vax1 rs7078160 polymorphisms in southern Han Chinese

IntroductionNon-syndromic cleft lip with or without cleft palate is a common worldwide birth defect due to a combination of environmental and genetic factors. Genome-wide association studies reported the rs7078160 of Vax1 is closely related to non-syndromic cleft lip with or without cleft palate in European populations. The following studies showed the same results in Mongolian, Japanese, Filipino, Vietnamese populations etc. However, conflicting research had been reported in Chinese population,ObjectiveThe aim of this study was to investigate the association between the rs7078160 polymorphism and non-syndromic cleft lip with or without cleft palate in Southern Chinese patients.MethodsIn this study, we investigated the polymorphism distribution of rs7078160 in 100 complete patient trios (39 patients with non-syndromic cleft lip and palate; 36 patients with non-syndromic cleft lip only; 25 had non-syndromic cleft palate only; and their parents) from Southern ethnic Han Chinese. 60 healthy trios were selected as control. Polymerase chain reaction and Sanger sequencing were used to genotype rs7078160 in Vax1; both case–control and family-based associations were analyzed.ResultsThe case–control analyses revealed the rs7078160 polymorphism was significant, associated with non-syndromic cleft lip with or without cleft palate (p = 0.04) and non-syndromic cleft lip and palate (p = 0.01), but not associated with non-syndromic cleft lip only and non-syndromic cleft palate only patients. The genotype composition of rs7078160 comprises mutated homozygous AA, heterozygous AG and wild homozygous GG. Cases with AG + AA genotypes compared with GG homozygotes showed an increased risk of non-syndromic cleft lip with or without cleft palate (p = 0.04, OR = 2.05, 95% CI: 1.01–4.16) and non-syndromic cleft lip and palate (p = 0.01, OR = 3.94, 95% CI: 1.34–11.54). In addition, we did not detect any transmission-disequilibrium in rs7078160 (p = 0.68).ConclusionThis study suggests that rs7078160 polymorphism is a risk factor of non-syndromic cleft lip with or without cleft palate, and Vax1 is strongly associated with non-syndromic cleft lip with or without cleft palate in Southern Chinese Han populations.     

Determination of [11C]PBR28 binding potential in vivo: a first human TSPO blocking study

Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BP_ND). Here, we used blockade of the TSPO radioligand [¹¹C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (V_ND), and hence estimate the BP_ND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [¹¹C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, V_ND was estimated via the occupancy plot. Values of BP_ND for all subjects were calculated using this V_ND estimate. Total volume of distribution (V_T) of MABs (2.94±0.31) was lower than V_T of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13 mg/kg). The occupancy plot provided a V_ND estimate of 1.98 (1.69, 2.26). Based on these V_ND estimates, BP_ND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [¹¹C]PBR28 V_ND and hence BP_ND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating V_ND for TSPO targeting radioligands.     

A genetic variant of PPARA modulates cardiovascular risk biomarkers after milk consumption

ObjectiveThe association of dairy food consumption with the risk for developing cardiovascular disease (CVD) has been investigated in many studies, but results often have been contradictory. The aim of the present study was to determine whether genetic polymorphisms are associated with interindividual variation in the response of CVD risk biomarker values after milk consumption.MethodsFourteen single nucleotide polymorphisms (SNPs) in nine genes related to lipid metabolism were examined in 161 volunteers randomly allocated to consume either 500 mL/d of skimmed (S) or semi-skimmed (SS) milk for 1 year in addition to their usual diets. Total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and low-density lipoprotein/HDL-C ratios were used as biomarkers of CVD risk. Three-way repeated-measures analysis of variance was used to examine the effect of time, treatment (S or SS), and genotype on these biomarkers.ResultsA TT genotype for the proliferator-activated receptor alpha polymorphism (PPARA rs135549 SNP) was significantly associated with a reduction in the TC/HDL and LDL/HDL ratios after 12 mo of S milk intake (mean reduction −0.29, 95% confidence interval [CI], −0.63 to 0.05; P = 0.0015 and −0.31, 95% CI, −0.58 to −0.03; P = 0.0005, respectively). However, no differences were observed after consuming either S or SS milk in the C allele carriers.ConclusionsSaturated fatty acid consumption has long been linked to an increased risk for CVD; indeed, the consumption of saturated fat-free products is recommended as a means of reducing this risk. However, the present results suggest that many individuals might not benefit from such general recommendations. Genetic analysis of PPARA rs135549 might help identify those individuals who are more likely to benefit from reducing the saturated fatty acid content of their diet.     

Relations between catechol-O-methyltransferase Val158Met genotype and inhibitory control development in childhood

The Val158Met rs4680 single-nucleotide polymorphism (SNP) at the catechol-O-methyltransferase (COMT) gene, primarily involved in dopamine breakdown within prefrontal cortex, has shown relations with inhibitory control (IC) in both adults and children. However, little is known about how COMT genotype relates to developmental trajectories of IC throughout childhood. Here, our study explored the effects of the COMT genotype (Val/Val, Val/Met, and Met/Met) on IC trajectories between the ages of 5 and 10 years. Children (n = 222) completed a Go/Nogo task at ages 5, 7, and 10; IC was characterized using signal detection theory to examine IC performance (d′) and response strategy (RS) (criterion). COMT genotype was not related to initial levels of IC performance and RS at age 5 or change in RS from ages 5 to 10. In contrast, COMT genotype was related to change in IC performance between 5 and 10 years. While Val/Val children did not differ from Val/Met children in development of IC performance, children with the Met/Met genotype exhibited more rapid development of IC performance when compared with Val/Met peers. These results suggest that COMT genotype modulates the development of IC performance in middle childhood.