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Associations between SLC16A11 variants and diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

ABSTRACT: Five sequence variants in SLC16A11 (rs117767867, rs13342692, rs13342232, rs75418188, and rs75493593), which occur in two non-reference haplotypes, were recently shown to be associated with diabetes in Mexicans from the SIGMA consortium. We aimed to determine whether these previous findings would replicate in the HCHS/SOL Mexican origin group and whether genotypic effects were similar in other HCHS/SOL groups. We analyzed these five variants in 2492 diabetes cases and 5236 controls from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), which includes U.S. participants from six diverse background groups (Mainland groups: Mexican, Central American, and South American; and Caribbean groups: Puerto Rican, Cuban, and Dominican). We estimated the SNP-diabetes association in the six groups and in the combined sample. We found that the risk alleles occur in two non-reference haplotypes in HCHS/SOL, as in the SIGMA Mexicans. The haplotype frequencies were very similar between SIGMA Mexicans and the HCHS/SOL Mainland groups, but different in the Caribbean groups. The SLC16A11 sequence variants were significantly associated with risk for diabetes in the Mexican origin group (P?=?0.025), replicating the SIGMA findings. However, these variants were not significantly associated with diabetes in a combined analysis of all groups, although the power to detect such effects was 85% (assuming homogeneity of effects among the groups). Additional analyses performed separately in each of the five non-Mexican origin groups were not significant. We also analyzed (1) exclusion of young controls and, (2) SNP by BMI interactions, but neither was significant in the HCHS/SOL data. The previously reported effects of SLC16A11 variants on diabetes in Mexican samples was replicated in a large Mexican-American sample, but these effects were not significant in five non-Mexican Hispanic/Latino groups sampled from U.S. populations. Lack of replication in the HCHS/SOL non-Mexicans, and in the entire HCHS/SOL sample combined may represent underlying genetic heterogeneity. These results indicate a need for future genetic research to consider heterogeneity of the Hispanic/Latino population in the assessment of disease risk, but add to the evidence suggesting SLC16A11 as a potential therapeutic target for type 2 diabetes.

SUBMITTER: Hidalgo BA

PROVIDER: S-EPMC6351621 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Sleep apnea and diabetes mellitus (DM) negatively impact cardiovascular health. One important indicator of cardiovascular health is the Ankle-Brachial Index (ABI). Either low ABI or high ABI are signs of peripheral vascular impairment. Impaired vascular health and DM, together, might provoke sleep apnea; however, information regarding these relationships is limited. Therefore, this study aimed to investigate the association between ABI, DM status, and severity of obstructive sleep apnea in people of Hispanic/Latino descent who are diverse in culture, environmental exposures, nativity, socioeconomic status, and disease burden. METHODS:A cross sectional analysis from a multi-center epidemiologic study, Hispanic Community Health Study/Study of Latinos, was utilized and included 3779 participants (mean age 55.32?±?7.67, females 57.9%). The sample was divided into 4 groups based on the American Diabetes Association diagnostic guidelines (no DM or DM), and the ABI status (normal and abnormal). Multiple linear regression analysis was used to determine the association of the four groups and other independent variables with severity of sleep apnea measured by apnea-hypopnea index. Kruskal-Wallis H test was used for comparisons between groups for the apnea-hypopnea index. The significant level was set at 0.01. RESULTS:There were significant differences between groups in the mean of apnea-hypopnea index (P?<?0.001; no DM?+?normal ABI?=?5.42?±?9.66, no DM?+?abnormal ABI?=?7.11?±?11.63, DM?+?normal ABI?=?10.99?±?15.16, DM?+?abnormal ABI?=?12.81?±?17.80). Linear regression showed that DM and abnormal ABI were significantly associated with severe sleep apnea (??=?3.25, P?=?0.001) after controlling for age, sex, BMI, income, education, alcohol use, cigarette use, hypertension or related medication, stroke and statin use. CONCLUSION:These findings suggest that people with DM and abnormal ABI were more likely to have high apnea-hypopnea index compared to the other groups. We observed gradual increasing in the severity of sleep apnea from low abnormality groups to high abnormality groups for Hispanic/Latino. Further work should elucidate the association of DM, abnormal ABI and sleep apnea with longer term outcomes, and replicate this work in different populations.

Project description:BackgroundHigher levels of moderate-to-vigorous physical activity have been associated with a lower risk of diabetes, but less is known about how daily step counts (steps/day) are associated with diabetes risk. Therefore, we examined the association of steps/day and step intensity with incident diabetes.MethodsWe included 6634 adults from the population-based prospective cohort Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (2008-2017). Cox proportional hazard models that accounted for complex survey design and sampling weights were used to estimate the association of baseline accelerometer-assessed steps/day and step intensity with 6-year risk of incident diabetes as hazard ratios (HR) and 95% confidence intervals (CI). We further examined whether the percent of intense steps at a given accumulation of steps/day was associated with diabetes risk, and if associations were modified by specific cohort characteristics.ResultsThe average age of cohort members was 39 years and 52% were female. Adults had an average of 8164 steps/day and spent 12 min/day in brisk ambulation (> 100 steps/min). Over 6 years of follow-up, there were 1115 cases of diabetes. There was a suggestive lower risk of diabetes with more steps/day- adults had a 2% lower risk per 1000 steps/day (HR = 0.98 (95% CI 0.95, 1.00)). Inverse associations between average steps/day and diabetes incidence were observed across many cohort characteristics, but most importantly among adults at high risk for diabetes - those who were older, or had obesity or prediabetes. Adults who accumulated 17 min/day in brisk ambulation compared to < 2 min/day had a 31% lower risk of diabetes (HR = 0.69 (95% CI 0.53, 0.89)). A greater percent of intense steps for a given accumulation of steps/day was associated with further risk reduction.ConclusionAdults who accumulate more daily steps may have a lower risk of diabetes. Accumulating more steps/day and greater step intensity appear to be important targets for preventing diabetes.

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Associations between SLC16A11 variants and diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

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