TBC1D1 [TBC1 (tre-2/USP6, BUB2, cdc16) domain family, member 1] is a Rab-GTPase-activating related protein implicated in regulating the trafficking of glucose transporter 4 (GLUT4 or SLC2A4) storage vesicles to the cell surface in response to insulin and AMPK-activating stimuli in skeletal muscle. Mutations in the human and mouse TBC1D1 genes confer risk of obesity or leanness. We identified five single nucleotide polymorphisms (SNPs) in the porcine TBC1D1 gene. One of them (FN677935:g.219G>A) was genotyped either by high resolution melting and PCR-RFLP analyses to study allele frequencies in a few pig breeds and evaluate association with meat production and carcass traits in five groups of sib-tested pigs of Italian Large White and Italian Duroc breeds. The g.219G>A SNP was associated (P < 0.05) with ham weight, back fat thickness and lean cuts content in Italian Large White and with visible intermuscular fat in Italian Duroc pigs.
The aim of this work was to verify whether polymorphisms in candidate genes for litter size segregate in Italian Large White (ITLW) pigs. We genotyped 120 sows that belonged to six different farms for 10 single nucleotide polymorphisms (SNPs) of 10 different genes. Polymorphisms in the chosen genes had already been associated with litter-size traits in other pig populations and were candidates for function and/or chromosomal location. The results indicated that the CLGN, pDAZL, and RFN4 SNPs were not segregating in the genotyped samples. The remaining seven markers were polymorphic with minor allele frequencies ranging from 0.10 (AFP) to 0.48 (RBP4). Because of the observed genetic variabilities in the investigated loci, the polymorphisms in the AFP, BMPR1B, CXCL10, ESR2, GNRHR, MAN2B2, and RBP4 genes can be considered suitable markers for association studies with litter-size traits in ITLW pigs.
Background Clinical decision-making in patients with relapsed refractory multiple myeloma (RRMM) is challenging and identification of patients who can benefit the most from a given therapy is of critical importance. The International Myeloma Working Group (IMWG) index is one of the most robust scores to evaluate frailty, and it has been validated for patients with newly diagnosed MM. However, little is known on its applicability in the setting of RRMM and of its relationships with patient-reported health-related quality of life (HRQoL). Objectives The primary objective of this study was to investigate whether the IMWG frailty score is able to detect distinct patient-reported HRQoL profiles in the setting of RRMM. A secondary objective was to assess the prevalence of patient-reported clinically important symptoms by frailty groups (ie., fit, intermediate-fit, and frail). Patients and Methods This was an international (Italy and UK) prospective cohort observational study that consecutively enrolled patients from 30 centers. The patients were eligible if they had received at least 1 prior therapy (but no more than 5) and had RRMM according to IMWG criteria. An additional inclusion criterion at the time of study entry was the availability of all variables incorporated into the IMWG frailty score to allow classification of patients in the following three groups: fit, intermediate-fit and frail. Baseline assessment of HRQOL was mandatory to be included in this study and patients completed a set of well-validated measures including the EORTC QLQ-C30 and its myeloma module (QLQ-MY20). The scores from EORTC QLQ-C30 and MY20 questionnaires were summarized by means and standard deviations, overall and by frailty group. Unadjusted differences in mean scores were compared between frailty groups. We also estimated the adjusted mean differences in HRQoL scores of respectively fit and intermediate groups vs frail patients, using a multivariable linear regression model, adjusting for a number of key potential confounders including: sex, education, time since diagnosis, number of previous lines of therapy, previous transplantation, currently receiving therapy, myeloma status (refractory vs relapsed only) and type of MM at diagnosis (secretory vs else). We also assessed the prevalence of clinically important symptoms, based on previously published evidence-based thresholds, by IMWG frailty group. Results Overall, 365 RRMM patients were enrolled between November 2017 and December 2018. Median age was of 69.7 years (IQR, 62.7-75.0) and 296 had received at least two previous lines of therapy. According to the IMWG frailty score evaluation at study entry, 192 (53%), 85 (23%) and 88 (24%) patients were classified as fit, intermediate-fit and frail. Each group was associated with a clearly distinct patient-reported HRQoL profile with both fit and intermediate-fit groups reporting statistically and clinically meaningful better outcomes (ie., improved functional status and lower symptom burden) than frail patients in the majority of the scales from the EORTC QLQ-C30 and QLQ-MY20. For example, mean scores of the EORTC QLQ-C30 physical functioning scale were 71.2, 62.2, and 47.5 for fit, intermediate-fit and frail patients, respectively (p<0.001) (i.e., higher score indicates better functioning). Similarly, the mean score of the QLQ-MY-20 disease symptoms scale was 22.8, 25.9 and 35.9 for fit, intermediate-fit and frail patients, respectively (p<0.001) (i.e., higher score indicates higher symptom burden). Adjusted mean score differences (resulting from multivariable analysis) confirmed clinically relevant differences across most scales of the EORTC QLQ-C30 and QLQ-MY20. Additionally, the prevalence of patient-reported clinically important symptoms was statistically significant different across the three IMWG frailty groups with regard to pain (p=0.002), dyspnea (p=0.004), fatigue (p<0.001), insomnia (p=0.022) constipation (p=0.003) and appetite loss (p=0.001). Details are reported in Figure. Conclusions: In the setting of RRMM, the IMWG frailty score is able to detect clearly distinct patient-reported HRQoL profiles. Current findings may lay the groundwork for the development of a patient-centered frailty index, which also incorporates HRQoL data, to be used in patients with RRMM treated in real-life. Figure 1 Figure 1. Disclosures Efficace: Janssen: Consultancy; Abbvie: Consultancy, Other: Grants (to Institution); Amgen: Consultancy, Other: Grants (to Institution); Takeda: Consultancy. Gaidano: Incyte: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astrazeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Petrucci: BMS: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Karyopharm: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board. Tafuri: Celgene: Research Funding; Roche: Research Funding; Novartis: Research Funding. Larocca: Amgen: Honoraria; Bristol-Myers Squibb: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; GSK: Honoraria; Takeda: Other: Advisory Board. Molica: Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Astrazeneca: Honoraria. Gozzetti: Janssen: Honoraria; AbbVie: Honoraria. Vignetti: Amgen: Consultancy, Honoraria; Incyte: Honoraria; Novartis: Honoraria. Cavo: Novartis: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
Many studies have reported that markers in the estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) genes are associated with litter size in pigs, even if inconsistent results have been obtained in different populations. We analysed the ESR1 PvuII and the ESR2 AF164957:c.949G>A polymorphisms in Italian Large White (ITLW) sows to evaluate if these markers are associated with number of piglets born alive at first litter (NBA1). First, both polymorphisms were genotyped by selective genotyping in a total of 440 sows chosen according to the extreme and divergent estimated breeding value (EBV) for NBA1 (220 sows with low EBV and 220 sows with high EBV). For the ESR1 polymorphism, no allele and genotype frequency differences were observed between the two groups (allele A=0.62 and allele B=0.38 in both two groups). For the ESR2 polymorphism, a trend of different allele frequency between the two tails was identified (P=0.052). However, no significant association between the same ESR2 marker and EBV NBA1 was detected analyzing 1772 ITLW sows (allele A=0.59 and allele G=0.41). As the two investigated polymorphisms were not associated with NBA1 EBVs, they seem not useful for marker assisted selection to improve this trait in the ITLW breed.
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