Synergistic Effect between the APOE ε4 Allele with Genetic Variants of GSK3B and MAPT: Differential Profile between Refractory Epilepsy and Alzheimer Disease.

Temporal Lobe Epilepsy (TLE) is a chronic neurological disorder characterized by recurrent focal seizures originating in the temporal lobe. Despite the variety of antiseizure drugs currently available to treat TLE, about 30% of cases continue to have seizures. The etiology of TLE is complex and multifactorial. Increasing evidence indicates that Alzheimer's disease (AD) and drug-resistant TLE present common pathological features that may induce hyperexcitability, especially aberrant hyperphosphorylation of tau protein. Genetic polymorphic variants located in genes of the microtubule-associated protein tau (MAPT) and glycogen synthase kinase-3ß (GSK3B) have been associated with the risk of developing AD. The APOE ε4 allele is a major genetic risk factor for AD. Likewise, a gene-dose-dependent effect of ε4 seems to influence TLE. The present study aimed to investigate whether the APOE ɛ4 allele and genetic variants located in the MAPT and GSK3B genes are associated with the risk of developing AD and drug-resistant TLE in a cohort of the Mexican population. A significant association with the APOE ε4 allele was observed in patients with AD and TLE. Additional genetic interactions were identified between this allele and variants of the MAPT and GSK3B genes.

Genomic diversity study of highly crossbred cattle population in a Low and Middle Tropical environment.

Milk production in tropical regions plays a crucial role both economically and socially. Typically, animals are utilized for dual purposes and are genetically obtained by an intense crossbreeding between Zebu and/or locally adapted breeds, alongside specialized breeds for dairy production. However, uncontrolled mating and crossbreeding may affect the establishment of an effective animal breeding program. The objective of this study was to evaluate Genomic diversity of highly crossbred cattle population in a Low and Middle Tropical environment. All sampled animals were genotyped using the Genessek GGP Bovine 100 chip (n = 859) and public genomic information from eight breeds were employed as reference. The genetic structure of the population was estimated using a Principal Component, Bayesian clustering and a linkage disequilibrium analysis. PCA results revealed that PC1 explained 44.39% of the variation, associated with the indicus/taurus differentiation, and PC2 explained 14.6% of the variation, attributed to the differentiation of Creole and European components. This analysis underscored a low population structure, attributed to the absence of genealogical tracking and the implementation of non-directed crossbreeding. The clustering shows an average contribution of Zebu, Creole, and European Taurine components in the population was 53.26%, 27.60%, and 19.13%, respectively. While an average LD of 0.096 was obtained for a maximum distance of 400 kb. The LD value was low in this population, probably due to the almost no selection applied and the recombination events that occurred during its development. These findings underscore the value of crossbreeding in tropical dairy production but emphasize the importance of directing the mattings.

Fruit juice and childhood obesity: a review of epidemiologic studies.

Childhood obesity is a national epidemic, and many efforts have been made to understand its risk factors. The purpose of this review was to provide an updated account of the observational studies evaluating the relationship between 100% fruit juice intake and obesity in children and adolescents, and to highlight the major risk factors that may impact this relationship. PubMed and Scopus were searched for terms related to fruit juice and childhood obesity, and studies assessing 100% fruit juice intake in participants ≤ 19 years old, with obesity-related outcomes (BMI or adiposity), and published before March 9, 2021 were included. There were 17 prospective cohort and 14 cross-sectional studies included in the analysis. Overall, the evidence does not support a relationship between 100% fruit juice intake and measures of obesity in most children. There is some evidence to suggest a minor positive association in some overweight or very young children, but due to fundamental differences and limitations in methodology, further investigation is required. Significant gaps in literature on this topic exist particularly in regards to randomized clinical trials in children, and in studies in racially diverse populations.

A New Texture Spectrum Based on Parallel Encoded Texture Unit and Its Application on Image Classification: A Potential Prospect for Vision Sensing.

In industrial applications based on texture classification, efficient and fast classifiers are extremely useful for quality control of industrial processes. The classifier of texture images has to satisfy two requirements: It must be efficient and fast. In this work, a texture unit is coded in parallel, and using observation windows larger than 3×3, a new texture spectrum called Texture Spectrum based on the Parallel Encoded Texture Unit (TS_PETU) is proposed, calculated, and used as a characteristic vector in a multi-class classifier, and then two image databases are classified. The first database contains images from the company Interceramic®® and the images were acquired under controlled conditions, and the second database contains tree stems and the images were acquired in natural environments. Based on our experimental results, the TS_PETU satisfied both requirements (efficiency and speed), was developed for binary images, and had high efficiency, and its compute time could be reduced by applying parallel coding concepts. The classification efficiency increased by using larger observational windows, and this one was selected based on the window size. Since the TS_PETU had high efficiency for Interceramic®® tile classification, we consider that the proposed technique has significant industrial applications.

Exercise and Protein Supplementation Recommendations for Older Adults With Sarcopenic Obesity: A Meta-Review.

This systematic meta-review evaluated the effects of exercise with and without protein interventions on muscle strength and function in older adults with sarcopenic obesity. PubMed, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, Scopus, and SPORTDiscus databases were searched through February 2021 for relevant systematic reviews and meta-analyses with aerobic, resistance, and/or combined training interventions with and without protein supplementation in older adults ≥ 65 years with sarcopenic obesity. This meta-review showed that exercise with and without protein supplementation improved body composition (i.e., decreased percentage body fat) and functional outcomes (i.e., gait speed and grip strength). Because the current literature is limited, determining the effects of exercise and combined protein supplementation in this population requires further investigation. In the meantime, protein recommendations should align with general sarcopenia recommendations. Based upon available findings, tentative exercise recommendations to optimize health outcomes in this population are proposed.

Bull sperm selection by attachment to hyaluronic acid semi-interpenetrated hydrogels.

We report the development of a hydrogel-based approach to select bull spermatozoa, a crucial step for successful assisted reproductive techniques (ARTs). Hyaluronic acid (HA) semi-interpenetrated N-isopropylacrylamide (PNIPAM) co-20% N-Tris (hydroxymethyl) methyl acrylamide (HMA) hydrogels were synthetized on glass surfaces and cultured in presence of frozen-thawed bull spermatozoa. A fraction of motile bull spermatozoa population strongly attached to hydrogels and was partially released by treatment with hyaluronidase. Fifty-nine (59 ± 7.24) per cent of sperm cells attached to PNIPAM-HMA-HA hydrogels and 31.16 ± 4.81% of them were released upon treatment with medium containing hyaluronidase. This attached-released sperm fraction has acceptable characteristics of progressive motility (50.0 ± 5.0%), vigour (4), high viability (58.7 ± 11.7%) and low percentage of acrosome reacted spermatozoa (23.36 ± 4.1%). Our findings indicate that PNIPAM-HMA-HA hydrogels are non-toxic and allow the selection of high-quality sperm cells for ART.

Physiological Limitations of Protein Foods Ounce Equivalents and the Underappreciated Role of Essential Amino Acid Density in Healthy Dietary Patterns.

Protein quality is an important component of protein intake to support growth, development, and maintenance of essential body tissues and functions. Therefore, protein quality should be emphasized as a key characteristic during protein food selection within the larger context of healthy dietary patterns, especially when considering the wide variance of protein quality across animal- and plant-based foods. However, the USDA Dietary Guidelines for Americans (DGA) do not address specific protein quality recommendations within their protein foods ounce equivalents guidance or as a component of Healthy U.S. Style, Healthy Vegetarian, and Healthy Mediterranean Style dietary patterns. In addition, the protein foods ounce equivalents within the DGA are not established on any obvious metabolic equivalency characteristic [i.e., energy, protein, or essential amino acid (EAA) content], which creates misleading messaging of equivalent functional and metabolic benefit across protein foods. EAA content is a key characteristic of protein quality and can be a practical focal point for protein intake recommendations and achieving healthy dietary patterns. This review discusses the importance of protein quality, the state of messaging within DGA recommendations, and proposes EAA density (i.e., EAA content relative to total energy) as one practical approach to improve current dietary recommendations. Two recent publications that evaluated the DGA protein foods ounce equivalents based on metabolic effect and their application within DGA recommended dietary patterns are discussed.

Working memory deficits in schizophrenia are associated with the rs34884856 variant and expression levels of the NR4A2 gene in a sample Mexican population: a case control study.

BACKGROUND: Cognitive functions represent useful endophenotypes to identify the association between genetic variants and schizophrenia. In this sense, the NR4A2 gene has been implicated in schizophrenia and cognition in different animal models and clinical trials. We hypothesized that the NR4A2 gene is associated with working memory performance in schizophrenia. This study aimed to analyze two variants and the expression levels of the NR4A2 gene with susceptibility to schizophrenia, as well as to evaluate whether possession of NR4A2 variants influence the possible correlation between gene expression and working memory performance in schizophrenia. METHODS: The current study included 187 schizophrenia patients and 227 controls genotyped for two of the most studied NR4A2 genetic variants in neurological and neuropsychiatric diseases. Genotyping was performed using High Resolution Melt and sequencing techniques. In addition, mRNA expression of NR4A2 was performed in peripheral mononuclear cells of 112 patients and 118 controls. A group of these participants, 54 patients and 87 controls, performed the working memory index of the WAIS III test. RESULTS: Both genotypic frequencies of the two variants and expression levels of the NR4A2 gene showed no significant difference when in patients versus controls. However, patients homozygous for the rs34884856 promoter variant showed a positive correlation between expression levels and auditory working memory. CONCLUSIONS: Our finding suggested that changes in expression levels of the NR4A2 gene could be associated with working memory in schizophrenia depending on patients' genotype in a sample from a Mexican population.

Influence of COMT polymorphism in cognitive performance on dementia in community-dwelling elderly Mexican (SADEM study).

There is an inconsistent finding about the relationship of catechol-O-methyltransferase (COMT) with dementia susceptibility, as well as with cognitive impairment. To substantiate this, we examined COMT genotype effects in certain cognitive domains in dementia. To evaluate the effects of COMT Val158Met on cognitive performance, we used The Mini-Mental State Examination (MMSE), the cognitive subscale of the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) and the Syndrome Kurz Test (SKT). The results show COMT Val/Met, Val/Val genotype polymorphisms had a significant effect on cognition performance (OR = 1.75 (95 %CI 1.22-2.54) and (OR = 2.76 (95 %CI 1.78-4.26), p < 0.001), and with adjustment for all cognitive test scores together, Val/Val (OR = 4.98 (95 % CI 1.47-16.86) and Val/Met (OR = 3.62 (95 % CI 1.37-9.56) had effect. Our study allows us to understand the role of COMT in cognitive performance in dementia, as well as interaction with other known risk factors for this pathology. This data might help in developing new therapeutic targets for cognitive impairment, main symptom of dementia. Other risk genotypes or haplotypes should be evaluated to determine the association with cognitive decline in dementia.

Testosterone supplementation upregulates androgen receptor expression and translational capacity during severe energy deficit.

Testosterone supplementation during energy deficit promotes whole body lean mass accretion, but the mechanisms underlying that effect remain unclear. To elucidate those mechanisms, skeletal muscle molecular adaptations were assessed from muscle biopsies collected before, 1 h, and 6 h after exercise and a mixed meal (40 g protein, 1 h postexercise) following 14 days of weight maintenance (WM) and 28 days of an exercise- and diet-induced 55% energy deficit (ED) in 50 physically active nonobese men treated with 200 mg testosterone enanthate/wk (TEST) or placebo (PLA) during the ED. Participants (n = 10/group) exhibiting substantial increases in leg lean mass and total testosterone (TEST) were compared with those exhibiting decreases in both of these measures (PLA). Resting androgen receptor (AR) protein content was higher and fibroblast growth factor-inducible 14 (Fn14), IL-6 receptor (IL-6R), and muscle ring-finger protein-1 gene expression was lower in TEST vs. PLA during ED relative to WM (P < 0.05). Changes in inflammatory, myogenic, and proteolytic gene expression did not differ between groups after exercise and recovery feeding. Mechanistic target of rapamycin signaling (i.e., translational efficiency) was also similar between groups at rest and after exercise and the mixed meal. Muscle total RNA content (i.e., translational capacity) increased more during ED in TEST than PLA (P < 0.05). These findings indicate that attenuated proteolysis at rest, possibly downstream of AR, Fn14, and IL-6R signaling, and increased translational capacity, not efficiency, may drive lean mass accretion with testosterone administration during energy deficit.

Genetic polymorphisms associated with pediatric-onset type 2 diabetes: A family-based transmission disequilibrium test and case-control study.

BACKGROUND AND OBJECTIVE: Genetics play a very strong role in the development of pediatric-onset type 2 diabetes (T2D); however, little information exists about specific common single nucleotide polymorphisms (SNPs) associated with T2D in this age group. The aim of the study was to analyze the association and parental transmission of 64 obesity-related SNPs with pediatric-onset T2D in Mexican families. METHODS: A total of 57 pedigrees containing 171 probands with pediatric-onset T2D and 119 unrelated controls older than 18 years were included. The participants were genotyped for 64 polymorphisms. Association of each variant with pediatric-onset T2D was analyzed through a parent-offspring transmission disequilibrium test (TDT) and in a case-control comparison by χ2 analysis. RESULTS: Five SNPs exhibited associations with pediatric-onset T2D in the combined case-parent trio and case-control analysis: LINGO/rs10968576 (odds ratio [OR] 1.82, P = 0.003), POC5/rs2112347 (OR 1.96, P = 2.4E-5), RPS10-NUDT3/rs206936 (OR 1.40, P = 0.023), GLIS3/rs7034200 (OR 2.34, P = 1.2E-6), and VEGFA/rs6905288 (OR 1.58, P = 0.015). The first three were also associated with obesity status. The SNPs POC5/rs2112347 and RPS10-NUDT3/rs206936 were significantly associated through the maternal allele and GLIS3/rs7034200 through the paternal allele (P < 0.05). CONCLUSIONS: These findings suggest that certain SNPs associated with obesity and other metabolic traits may also be involved in risk of pediatric-onset T2D in Mexican families. We also identified preferential transmission of parental alleles in some variants.

Modeling hind-limb kinematics using a bio-inspired algorithm with a local search.

BACKGROUND: Laboratory rats play a critical role in research because they provide a biological model that can be used for evaluating the affectation of diseases and injuries, and for the evaluation of the effectiveness of new drugs and treatments. The analysis of locomotion in laboratory rats facilitates the understanding of motor defects in many diseases, as well as the damage and recovery after peripheral and central nervous system injuries. However, locomotion analysis of rats remains a great challenge due to the necessity of labor intensive manual annotations of video data required to obtain quantitative measurements of the kinematics of the rodent extremities. In this work, we present a method that is based on the use of a bio-inspired algorithm that fits a kinematic model of the hind limbs of rats to binary images corresponding to the segmented marker of images corresponding to the rat's gait. The bio-inspired algorithm combines a genetic algorithm for a group of the optimization variables with a local search for a second group of the optimization variables. RESULTS: Our results indicate the feasibility of employing the proposed approach for the automatic annotation and analysis of the locomotion patterns of the posterior extremities of laboratory rats. CONCLUSIONS: The adjustment of the hind limb kinematic model to markers of the video frames corresponding to rat's gait sequences could then be used to analyze the motion patterns during the steps, which, in turn, can be useful for performing quantitative evaluations of the effect of lesions and treatments on rats models.

Routine Yoga Practice Impacts Whole Body Protein Utilization in Healthy Women.

Whole body protein utilization (WBPU), which includes flux (Q), protein synthesis (PS), protein breakdown (PB), and whole body protein balance (WBPB), provides insight regarding muscle mass, a criterion for sarcopenia. To characterize yoga's impact on WBPU, body composition and functional measures in healthy (50-65 years) women. WBPU and functional measures were compared between women who routinely practiced yoga (YOGA; n = 7) and nonactive counterparts (CON; n = 8). Q (0.61 ± 0.06 vs. 0.78 ± 0.07, p = .04), PS (3.07 ± 0.37 vs. 4.17 ± 0.40, p = .03), PB (2.59 ± 0.48 vs. 3.80 ± 0.48, p = .05) were lower, and lean body mass higher (64 ± 1 vs. 58 ± 2%, p ≤ .01) for YOGA vs. CON, respectively. WBPB and functional measures were similar. Routine yoga practice influenced WBPU in healthy older women. Study findings are novel and provide a basis for future investigations evaluating long-term benefits of yoga as an alternative mode of exercise for maintaining muscle mass in support of active aging.

Polymorphisms of APLN-APLNR system are associated with essential hypertension in Mexican-Mestizo individuals.

The aim of this study was to evaluate if polymorphisms of APLN and APLNR genes may play a role as susceptibility markers for hypertension in a group of Mexican-Mestizo patients. A case-control study was carried out including normotensive and hypertensive individuals. For these, two polymorphisms of APLN (rs3761581 and rs56204867) and two of APLNR () genes were genotyped by 5' exonuclease TaqMan assay in 400 normotensive individuals and 383 patients. The results showed that, under an additive model adjusted by BMI, HDL, triglycerides, glucose and family history of essential hypertension, the rs7119375 and rs10501367 polymorphisms of APLNR gene were associated significantly with a decreased risk of essential hypertension (P=0.039 and P=0.029, respectively). Besides, the haplotypes analysis of these polymorphisms showed that H1 haplotype was associated with an increased risk of essential hypertension (P=0.026), while the H2 haplotype was associated with a decreased risk (P=0.032). Contrary, the rs3761581 and rs56204867 polymorphisms of APLN gene were not associated with essential hypertension (P=0.1707 and P=0.0769, respectively). The data suggest that APLNR rs7119375 and rs10501367 are associated with a decreased risk of essential hypertension in our Mexican-Mestizo studied group, but further studies are warranted.

Exogenous enzymes upgrade transgenesis and genetic engineering of farm animals.

Transgenic farm animals are attractive alternative mammalian models to rodents for the study of developmental, genetic, reproductive and disease-related biological questions, as well for the production of recombinant proteins, or the assessment of xenotransplants for human patients. Until recently, the ability to generate transgenic farm animals relied on methods of passive transgenesis. In recent years, significant improvements have been made to introduce and apply active techniques of transgenesis and genetic engineering in these species. These new approaches dramatically enhance the ease and speed with which livestock species can be genetically modified, and allow to performing precise genetic modifications. This paper provides a synopsis of enzyme-mediated genetic engineering in livestock species covering the early attempts employing naturally occurring DNA-modifying proteins to recent approaches working with tailored enzymatic systems.

On an integro-differential model for pest control in a heterogeneous environment.

Insect pests pose a major threat to a balanced ecology as it can threaten local species as well as spread human diseases; thus, making the study of pest control extremely important. In practice, the sterile insect release method (SIRM), where a sterile population is introduced into the wild population with the aim of significantly reducing the growth of the population, has been a popular technique used to control pest invasions. In this work we introduce an integro-differential equation to model the propagation of pests in a heterogeneous environment, where this environment is divided into three regions. In one region SIRM is not used making this environment conducive to propagation of the insects. A second region is the eradication zone where there is an intense release of sterile insects, leading to decay of the population in this region. In the final region we explore two scenarios. In the first case, there is a small release of sterile insects and we prove that if the eradication zone is sufficiently large the pests will not invade. In the second case, when SIRM is not used at all in this region we show that invasions always occur regardless of the size of the eradication zone. Finally, we consider the limiting equation of the integro-differential equation and prove that in this case there is a critical length of the eradication zone which separates propagation from obstruction. Moreover, we provide some upper and lower bound for the critical length.

High-resolution HLA analysis of primary and secondary Sjögren's syndrome: a common immunogenetic background in Mexican patients.

To compare the distribution of HLA-A, B, DRB1 and DQB1 alleles among Mexican patients with primary Sjögren Syndrome (pSS), secondary SS (sSS), connective tissue disease (CTD) without (w/o) SS and historical ethnically healthy controls. We included 28 pSS, 30 sSS, 96 CTD w/o SS patients and 234 controls. HLA-A, B, DRB1 and DQB1 were amplified and sequenced using the Allele SEQR Sequenced Based Typing Kits and analyzed on the ABI Prism*3130 DNA Analyzer using the Assign software. Gene frequencies were obtained by direct counting. Contingence tables of 2 × 2 were generated and analyzed by the Mantel-Haenzel χ (2) or Fisher's test (EPIINFO program). We reported odds ratios (OR) and corrected p values. SS patients showed increased frequencies of A*68:01 and DRB1*14:06 alleles when compared to CTD w/o SS (OR 4.43, 95 % CI 1.35-14.14, p = 0.007 and OR 14, 95 % CI 1.68-116, p = 0.001, respectively) and a higher prevalence of DRB1*01:01 (OR 5.9, 95 % CI 2.13-16.56, p = 0.003) and HLA-B*35:01 (OR 3.70, 95 % CI 1.92-7.12, p = 0.004) when compared with controls. pSS patients had a higher frequency of DRB1*14:06 allele than sSS (OR 16, 95 % CI 1.59-390, p = 0.001). Anti-Ro/SSA positivity was associated with B*51:01 (OR 10.11, 95 % CI 1.09-245, p = 0.02) and DRB1*03:01 alleles (OR 4.26, 95 % CI 1.01-18.89, p = 0.029), whereas the A*01:01 allele was associated with anti-La/SSB positivity (OR 4.75, 95 % CI 1.32-16.92, p = 0.003). In our population, the DRB1*14:06 allele was associated with primary and secondary SS implying that both varieties bear a similar immunogenetic background.

Hydration Status and Sodium Balance of Endurance Runners Consuming Postexercise Supplements of Varying Nutrient Content.

Postexercise protein and sodium supplementation may aid recovery and rehydration. Preserved beef provides protein and contains high quantities of sodium that may alter performance related variables in runners. The purpose of this study was to determine the effects of consuming a commercial beef product postexercise on sodium and water balance. A secondary objective was to characterize effects of the supplementation protocols on hydration, blood pressure, body mass, and running economy. Eight trained males (age = 22 ± 3 y, VO2max = 66.4 ± 4.2 ml·kg-1·min-1) completed three identical weeks of run training (6 run·wk-1, 45 ± 6 min·run-1, 74 ± 5% HRR). After exercise, subjects consumed either, a beef nutritional supplement (beef jerky; [B]), a standard recovery drink (SRD), or SRD+B in a randomized counterbalanced design. Hydration status was assessed via urinary biomarkers and body mass. No main effects of treatment were observed for 24 hr urine volume (SRD, 1.7 ± 0.5; B, 1.8 ± 0.6; SRD+B, 1.4 ± 0.4 L·d-1), urine specific gravity (1.016 ± 0.005, 1.018 ± 0.006, 1.017 ± 0.006) or body mass (68.4 ± 8.2, 68.3 ± 7.7, 68.2 ± 8.1 kg). No main effect of treatment existed for sodium intake-loss (-713 ± 1486; -973 ± 1123; -980 ± 1220 mg·d-1). Mean arterial pressure (81.0 ± 4.6, 81.1 ± 7.3, 83.8 ± 5.4 mm Hg) and average exercise running economy (VO2: SRD, 47.9 ± 3.2; B, 47.2 ± 2.6; SRD+B, 46.2 ± 3.4 ml·kg-1·min-1) was not affected. Urinary sodium excretion accounted for the daily sodium intake due to the beef nutritional supplement. Findings suggest the commercial beef snack is a viable recovery supplement following endurance exercise without concern for hydration status, performance decrements, or cardiovascular consequences.

Oropharyngeal administration of mother's milk to prevent necrotizing enterocolitis in extremely low-birth-weight infants: theoretical perspectives.

The oropharyngeal administration of mother's milk-placing drops of milk onto the infant's oral mucosa-may serve as a preventative strategy against necrotizing enterocolitis (NEC) for extremely low-birth-weight (ELBW: birth weight <1000 g) infants. Necrotizing enterocolitis is a devastating gastrointestinal disorder which is associated with significant mortality for ELBW infants. Survivors are at risk for costly and handicapping morbidities, including severe neurological impairment. The oropharyngeal administration of mother's milk to ELBW infants may serve to expose the infant's oropharynx to protective (immune and trophic) biofactors (also present in amniotic fluid) and may protect the infant against NEC. Emerging evidence suggests that this intervention may have many benefits for extremely premature infants including protection against bacteremia, NEC, and ventilator-associated pneumonia, an earlier attainment of full enteral feeds, enhanced maturation of oral feeding skills, improved growth, and enhanced breast-feeding outcomes. While more research is needed to definitively establish safety and efficacy of this intervention, this article will examine biological plausibility and will describe the theoretical mechanisms of protection against NEC for ELBW infants who receive this intervention. Nurses play a key role in advancing the science and practice of this intervention. Future directions for research and implications for nursing practice will also be presented.

Mismatch on glutathione S-transferase T1 increases the risk of graft-versus-host disease and mortality after allogeneic stem cell transplantation.

Several drug-metabolizing enzymes, preferentially expressed in the liver, have the potential to act as minor histocompatibility antigens. In the present study, we analyzed the impact of glutathione S-transferase T1 (GSTT1), glutathione S-transferase M1, glutathione S-transferase P1, and UDP glucuronosyl transferase 2B17 (UGT2B17) disparities on the outcome of 125 patients undergoing allogeneic hematopoietic stem cell transplantation. Grades 2 to 4 acute graft-versus-host disease (aGVHD) developed in 56.2% versus 73.3% of GSTT1-matched versus mismatched patients (P = .048). Remarkably, 8.6% GSTT1-matched patients developed grades 2 to 4 liver aGVHD, compared with 36.8% among GSTT1-mismatched recipients (P < .001). Regarding chronic graft-versus-host disease (cGVHD), 34.8% versus 70.7% matched versus mismatched patients developed overall cGVHD (P = .038) and 16.3% versus 48% developed hepatic cGVHD (P = .006). We also found a strong association between the UGT2B17 mismatch and the risk of severe aGVHD (P = .001), especially with gut involvement (P < .001). Most striking was the influence of the GSTT1 mismatch on nonrelapse mortality (26.8% versus 52.6%, P = .031) and overall survival (62% versus 36.9%, P = .045). In summary, UGT2B17 and GSTT1 mismatch are risk factors for the development of GVHD and the latter also influences on mortality and survival after allogeneic transplantation from HLA-identical donors.