Elevated serum urate levels can cause gout, an excruciating disease with suboptimal treatment. Previous GWAS identified common variants with modest effects on serum urate. Here we report large-scale whole-exome sequencing association studies of serum urate and kidney function among ≤19,517 European ancestry and African-American individuals. We identify aggregate associations of low-frequency damaging variants in the urate transporters SLC22A12 (URAT1; p = 1.3 × 10−56) and SLC2A9 (p = 4.5 × 10−7). Gout risk in rare SLC22A12 variant carriers is halved (OR = 0.5, p = 4.9 × 10−3). Selected rare variants in SLC22A12 are validated in transport studies, confirming three as loss-of-function (R325W, R405C, and T467M) and illustrating the therapeutic potential of the new URAT1-blocker lesinurad. In SLC2A9, mapping of rare variants of large effects onto the predicted protein structure reveals new residues that may affect urate binding. These findings provide new insights into the genetic architecture of serum urate, and highlight molecular targets in SLC22A12 and SLC2A9 for lowering serum urate and preventing gout.

PurposeSocial capital is a well-established predictor of several behavioral health outcomes. However, we know less about the relationship with prevention, transmission, and treatment of HIV/AIDS outcomes in the United States (US).MethodsIn 2017, we conducted a scoping review of empirical studies investigating the relationships between social capital and HIV/AIDS in the US by searching PubMed, Embase, PsycINFO, Web of Science, and Sociological Abstracts with no restriction on publication date, for articles in English language. Sample search terms included: HIV infections OR HIV OR AIDS OR acquired immunodeficiency syndrome OR human immunodeficiency virus AND social capital OR social control, informal OR social participation OR social cohesion OR generalized trust OR social trust OR collective efficacy OR community mob* OR civic participation.ResultsWe identified 1581 unique manuscripts and reviewed 13 based on eligibility criteria. The earliest eligible study was published in 2003. More than half (n=7/13) focused on HIV or AIDS diagnosis, then prescribing ART and/or adherence (n=5/13), then linkage and or engagement in HIV care (n=4/13). Fifty eight percent (58%) documented a protective association between at least one social capital measure and an HIV/AIDS outcome. Seven studies used validated social capital scales, however there was substantial variation in conceptual/operational definitions and measures used. Most studies were based on samples from the Northeast. Three studies directly focused on or stratified analyses among subgroups or key populations. Studies were cross-sectional, so causal inference is unknown.ConclusionOur review suggests that social capital may be an important determinant of HIV/AIDS prevention, transmission, and treatment outcomes. We recommend future research assess these associations using qualitative and mixed-methods approaches, longitudinally, examine differences across subgroups and geographic region, include a wider range of social capital constructs, and examine indicators beyond HIV diagnosis, as well as how mechanisms like stigma link social capital to HIV/AIDS.

IntroductionCancer-related fatigue (CRF) is the most uncomfortable symptom among women with a history of breast cancer. Black women are more likely than women of other racial/ethnic groups to have CRF risk factors, such as physical inactivity and obesity, yet CRF studies have not focused on black women. We conducted a cross-sectional analysis to assess CRF and physical activity among black women survivors of breast cancer.MethodIn May and July of 2012, 267 members (mean age, 54 y) of the Sisters Network, Inc, completed an online survey of sociodemographic characteristics, medical characteristics, and physical activity, and a fatigue instrument (the Functional Assessment of Chronic Illness Therapy [FACIT]). Multiple linear regression assessed fatigue and physical activity compliance (ie, 150 minutes of moderate to vigorous physical activity per week).ResultsParticipants had an average FACIT score of 32.3, Fatigue was greater (P < .001) among the 56% of women not meeting physical activity guidelines. In multivariable analysis, correlates of fatigue showed that physical activity compliance (β = 3.20, P < .001) and older age group (50–59 y: β = 3.98, P = .001; ≥60 y,: β = 3.76, P = .003) were associated with less fatigue. The interaction between age and fatigue was also significant: mean differences in fatigue by physical activity level were obvious only among women younger than 50 years. (P < .001).ConclusionPhysical activity compliance was associated with a lower level of fatigue. However, the effect of physical activity on fatigue may differ by age. Interventions aimed at curbing CRF in black women should consider age-appropriate strategies that can be integrated into existing lifestyles.

Purpose: Cancer-related fatigue is the most discomforting symptom among women with a history of breast cancer. Black women are more likely to experience risk factors for cancer-related fatigue, like physical inactivity and obesity, yet cancer-related fatigue studies have not explicitly focused on Black women. This cross-sectional analysis assesses cancer-related fatigue and physical activity among Black female breast cancer survivors. Methods: In May and July of 2012, 266 members of the Sisters Network, Inc completed an online survey on: demographics, cancer history and treatment, fatigue using the 13-item Function Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale, and engagement in ≥150 minutes per week of physical activity (CDC guideline). Multiple linear regression assessed relationships between fatigue and physical activity. Results: The average participant was 54 (SD=9) with a FACIT score of 13.63, indicating “severe fatigue”. Fatigue was greater (p=0.02) among the 56% of women meeting physical activity guidelines. Multivariable analysis showed that meeting physical activity guidelines (β=-3.01, p=0.01) and higher age group (50-59: -4.75, p=0.001; 60+: -4.38, p=0.01) were associated with greater fatigue. An interaction plot showed that differences in fatigue for those meeting or not meeting physical activity guidelines is largest among Black women under age 50. Conclusions: Meeting physical activity guidelines was associated with greater cancer-related fatigue, which was most pronounced for those under age 50. Interventions for Black breast cancer survivors with cancer-related fatigue should consider physical activities that can be integrated into existing tasks and provide age-appropriate resources to address physical and emotional fatigue domains. Keywords: breast cancer; fatigue; age; Black/African-American; physical activity Citation Format: Melody A. Swen, Amandeep Mann, Raheem Paxton, Lorraine T. Dean. Cancer-related fatigue and physical activity vary by age for black women with a history of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4215. doi:10.1158/1538-7445.AM2017-4215