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Susceptibility variants for waist size in relation to abdominal, visceral, and hepatic adiposity in postmenopausal women.

ABSTRACT: Genome-wide association studies have identified common genetic variants that can contribute specifically to the risk of abdominal adiposity, as measured by waist circumference or waist-to-hip ratio. However, it is unknown whether these genetic risk factors affect relative body fat distribution in the abdominal visceral and subcutaneous compartments. The association between imaging-based abdominal fat mass and waist-size risk variants in the FTO, LEPR, LYPLAL1, MSRA, NRXN3, and TFAP2B genes was investigated. A cross-sectional sample of 60 women was selected among study participants of The Multiethnic Cohort, who were aged 60 to 65 years, of European or Japanese descent, and with a body mass index (calculated as kg/m(2)) between 18.5 and 40. Dual-energy x-ray absorptiometry and abdominal magnetic resonance imaging scans were used to measure adiposity. After adjustments for age, ethnicity, and total fat mass, the FTO variants showed an association with less abdominal subcutaneous fat and a higher visceral-to-subcutaneous abdominal fat ratio, with the variant rs9941349 showing significant associations most consistently (P=0.003 and 0.03, respectively). Similarly, the LEPR rs1137101 variant was associated with less subcutaneous fat (P=0.01) and a greater visceral-to-subcutaneous fat ratio (P=0.03) and percent liver fat (P=0.007). MSRA rs545854 variant carriers had a lower percent of leg fat. Our findings provide initial evidence that some of the genetic risk factors identified for larger waist size might also contribute to disproportionately greater intra-abdominal and liver fat distribution in postmenopausal women. If replicated, these genetic variants can be incorporated with other biomarkers to predict high-risk body fat distribution.

SUBMITTER: Lim U

PROVIDER: S-EPMC3419359 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Susceptibility variants for waist size in relation to abdominal, visceral, and hepatic adiposity in postmenopausal women.

Lim Unhee U Ernst Thomas T Wilkens Lynne R LR Albright Cheryl L CL Lum-Jones Annette A Seifried Ann A Buchthal Steven D SD Novotny Rachel R Kolonel Laurence N LN Chang Linda L Cheng Iona I Le Marchand Loïc L

Journal of the Academy of Nutrition and Dietetics 20120701 7

Genome-wide association studies have identified common genetic variants that can contribute specifically to the risk of abdominal adiposity, as measured by waist circumference or waist-to-hip ratio. However, it is unknown whether these genetic risk factors affect relative body fat distribution in the abdominal visceral and subcutaneous compartments. The association between imaging-based abdominal fat mass and waist-size risk variants in the FTO, LEPR, LYPLAL1, MSRA, NRXN3, and TFAP2B genes was i ...[more]

PMID: 22889634

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Project description:BackgroundCharacterization of abdominal and intra-abdominal fat requires imaging, and thus is not feasible in large epidemiologic studies.ObjectiveWe investigated whether biomarkers may complement anthropometry (body mass index [BMI], waist circumference [WC], and waist-hip ratio [WHR]) in predicting the size of the body fat compartments by analyzing blood biomarkers, including adipocytokines, insulin resistance markers, sex steroid hormones, lipids, liver enzymes and gastro-neuropeptides.MethodsFasting levels of 58 blood markers were analyzed in 60 healthy, Caucasian or Japanese American postmenopausal women who underwent anthropometric measurements, dual energy X-ray absorptiometry (DXA), and abdominal magnetic resonance imaging. Total, abdominal, visceral and hepatic adiposity were predicted based on anthropometry and the biomarkers using Random Forest models.ResultsTotal body fat was well predicted by anthropometry alone (R(2) = 0.85), by the 5 best predictors from the biomarker model alone (leptin, leptin-adiponectin ratio [LAR], free estradiol, plasminogen activator inhibitor-1 [PAI1], alanine transaminase [ALT]; R(2) = 0.69), or by combining these 5 biomarkers with anthropometry (R(2) = 0.91). Abdominal adiposity (DXA trunk-to-periphery fat ratio) was better predicted by combining the two types of predictors (R(2) = 0.58) than by anthropometry alone (R(2) = 0.53) or the 5 best biomarkers alone (25(OH)-vitamin D(3), insulin-like growth factor binding protein-1 [IGFBP1], uric acid, soluble leptin receptor [sLEPR], Coenzyme Q10; R(2) = 0.35). Similarly, visceral fat was slightly better predicted by combining the predictors (R(2) = 0.68) than by anthropometry alone (R(2) = 0.65) or the 5 best biomarker predictors alone (leptin, C-reactive protein [CRP], LAR, lycopene, vitamin D(3); R(2) = 0.58). Percent liver fat was predicted better by the 5 best biomarker predictors (insulin, sex hormone binding globulin [SHBG], LAR, alpha-tocopherol, PAI1; R(2) = 0.42) or by combining the predictors (R(2) = 0.44) than by anthropometry alone (R(2) = 0.29).ConclusionThe predictive ability of anthropometry for body fat distribution may be enhanced by measuring a small number of biomarkers. Studies to replicate these data in men and other ethnic groups are warranted.

Project description:BackgroundStudies have suggested a link between alcohol intake and adiposity. However, results from longitudinal studies have been inconsistent, and a possible interaction with genetic predisposition to adiposity measures has often not been taken into account.ObjectiveTo examine the association between alcohol intake recorded at baseline and subsequent annual changes in body weight (∆BW), waist circumference (ΔWC) and WC adjusted for BMI (ΔWCBMI), and to test for interaction with genetic predisposition scores based on single nucleotide polymorphisms (SNPs) associated with various forms of adiposity.MethodThis study included a total of 7028 adult men and women from MONICA, the Diet, Cancer and Health cohort (DCH), and the Inter99 studies. We combined 50 adiposity-associated SNPs into four scores indicating genetic predisposition to BMI, WC, WHRBMI and all three traits combined. Linear regression was used to examine the association of alcohol intake (drinks of 12 g (g) alcohol/day) with ΔBW, ΔWC, and ΔWCBMI, and to examine possible interactions with SNP-scores. Results from the analyses of the individual cohorts were combined in meta-analyses.ResultsEach additional drink/day was associated with a ΔBW/year of -18.0 g (95% confidence interval (CI): -33.4, -2.6, P = 0.02) and a ΔWC of -0.3 mm/year (-0.5, -0.0, P = 0.03). In analyses of women only, alcohol intake was associated with a higher ΔWCBMI of 0.5 mm/year (0.2, 0.9, P = 0.002) per drink/day. Overall, we found no statistically significant interactions between the four SNP-scores and alcohol intake in relation to changes in adiposity measures. However in analyses of women separately, we found interaction between the complete score of all 50 SNPs and alcohol intake in relation to ΔBW (P for interaction = 0.03). No significant interaction was observed among the men.ConclusionAlcohol intake was associated with a decrease in BW and WC among men and women, and an increase in WCBMI among women only. We found no strong indication that these associations depend on a genetic predisposition to adiposity.Trial registrationRegistry: ClinicalTrials.gov Trial number: CT00289237 , Registered: 19 September 2005 retrospectively registered.

Project description:Background & aimsWe compared fat storage in the abdominal region among individuals from 5 different ethnic-racial groups to determine whether fat storage is associated with disparities observed in metabolic syndrome and other obesity-associated diseases.MethodsWe collected data from 1794 participants in the Multiethnic Cohort Study (60-77 years old; of African, European [white], Japanese, Latino, or Native Hawaiian ancestry) with body mass index values of 17.1-46.2 kg/m2. From May 2013 through April 2016, participants visited the study clinic to undergo body measurements, an interview, and a blood collection. Participants were evaluated by dual-energy x-ray absorptiometry and abdominal magnetic resonance imaging. Among ethnic groups, we compared adiposity of the trunk, intra-abdominal visceral cavity, and liver, adjusting for total fat mass; we evaluated the association of adult weight change with abdominal adiposity; and we examined the prevalence of metabolic syndrome mediated by abdominal adiposity.ResultsRelative amounts of trunk, visceral, and liver fat varied significantly with ethnicity-they were highest in Japanese Americans, lowest in African Americans, and intermediate in the other groups. Compared with African Americans, the mean visceral fat area was 45% and 73% greater in Japanese American men and women, respectively, and the mean measurements of liver fat were 61% and 122% greater in Japanese American men and women. The visceral and hepatic adiposity associated with weight gain since participants were 21 years old varied in a similar pattern among ethnic-racial groups. In the mediation analysis, visceral and liver fat jointly accounted for a statistically significant fraction of the difference in metabolic syndrome prevalence, compared with white persons, for African Americans, Japanese Americans, and Native Hawaiian women, independently of total fat mass.ConclusionsIn an analysis of data from the participants in the Multiethnic Cohort Study, we found extensive differences among ethnic-racial groups in the propensity to store fat intra-abdominally. This observation should be considered by clinicians in the prevention and early detection of metabolic disorders.

Project description:BackgroundSubclinical atherosclerosis identification remains challenging; abdominal visceral adiposity may improve risk stratification beyond traditional cardiovascular risk factors. Hypertriglyceridemic waist, a visceral adiposity marker combining elevated triglycerides (?2 mmol/L) and waist circumference (?90 cm), has been related to carotid atherosclerosis, although associations with high-risk features, including lipid-rich necrotic core (LRNC), remain unknown. We tested the hypothesis that hypertriglyceridemic waist is an independent marker of high-risk atherosclerosis features.Methods and resultsIn this cross-sectional study including 467 white men (mean age, 45.9±14.8 years; range 19.4-77.6 years), carotid atherosclerosis characteristics were examined by magnetic resonance imaging and associations with hypertriglyceridemic waist and benefits beyond Framingham Risk Score (FRS) and Pathobiological Determinants of Atherosclerosis in Youth (PDAY) were determined. Subclinical carotid atherosclerosis was present in 61.9% of participants, whereas 50.1% had LRNC. Hypertriglyceridemic waist was associated with carotid maximum wall thickness (P=0.014), wall volume (P=0.025), normalized wall index (P=0.004), and Carotid Atherosclerosis Score (derived from wall thickness and LRNC; P=0.049). Hypertriglyceridemic waist was associated with carotid LRNC volume beyond FRS (P=0.037) or PDAY (P=0.015), contrary to waist circumference alone (both P>0.05). Although 69.7% and 62.0% of participants with carotid atherosclerosis and/or LRNC were not high-risk by FRS or PDAY, respectively, hypertriglyceridemic waist correctly reclassified 9.7% and 4.5% of them, respectively. Combining hypertriglyceridemic waist with FRS (net reclassification improvement=0.17; P<0.001) or PDAY (net reclassification improvement=0.05; P=0.003) was superior to each score alone in identifying individuals with carotid atherosclerosis and/or LRNC.ConclusionsHypertriglyceridemic waist is an independent marker of carotid high-risk atherosclerosis features in men, improving on FRS and PDAY risk score.

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Susceptibility variants for waist size in relation to abdominal, visceral, and hepatic adiposity in postmenopausal women.

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Susceptibility variants for waist size in relation to abdominal, visceral, and hepatic adiposity in postmenopausal women.

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