Generalization of adiposity genetic loci to US Hispanic women.

BACKGROUND: Obesity is a public health concern. Yet the identification of adiposity-related genetic variants among United States (US) Hispanics, which is the largest US minority group, remains largely unknown. OBJECTIVE: To interrogate an a priori list of 47 (32 overall body mass and 15 central adiposity) index single-nucleotide polymorphisms (SNPs) previously studied in individuals of European descent among 3494 US Hispanic women in the Women's Health Initiative SNP Health Association Resource (WHI SHARe). DESIGN: Cross-sectional analysis of measured body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were inverse normally transformed after adjusting for age, smoking, center and global ancestry. WC and WHR models were also adjusted for BMI. Genotyping was performed using the Affymetrix 6.0 array. In the absence of an a priori selected SNP, a proxy was selected (r(2)0.8 in CEU). RESULTS: Six BMI loci (TMEM18, NUDT3/HMGA1, FAIM2, FTO, MC4R and KCTD15) and two WC/WHR loci (VEGFA and ITPR2-SSPN) were nominally significant (P<0.05) at the index or proxy SNP in the corresponding BMI and WC/WHR models. To account for distinct linkage disequilibrium patterns in Hispanics and further assess generalization of genetic effects at each locus, we interrogated the evidence for association at the 47 surrounding loci within 1 Mb region of the index or proxy SNP. Three additional BMI loci (FANCL, TFAP2B and ETV5) and five WC/WHR loci (DNM3-PIGC, GRB14, ADAMTS9, LY86 and MSRA) displayed Bonferroni-corrected significant associations with BMI and WC/WHR. Conditional analyses of each index SNP (or its proxy) and the most significant SNP within the 1 Mb region supported the possible presence of index-independent signals at each of these eight loci as well as at KCTD15. CONCLUSION: This study provides evidence for the generalization of nine BMI and seven central adiposity loci in Hispanic women. This study expands the current knowledge of common adiposity-related genetic loci to Hispanic women.

Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study.

SUMMARY: The Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D(3) daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer. INTRODUCTION: This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality. METHODS: WHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS). RESULTS: Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38-1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44-0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive. CONCLUSION: Though based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.

Use of the Pelvic Organ Prolapse staging system of the International Continence Society, American Urogynecologic Society, and Society of Gynecologic Surgeons in perimenopausal women.

OBJECTIVES: This study was undertaken to apply the standardized Pelvic Organ Prolapse staging system to perimenopausal women to obtain normative data and to determine any effects of risk factors for incontinence and prolapse on Pelvic Organ Prolapse staging system scores. STUDY DESIGN: Two hundred forty-one women aged 45 to 55 years who were seen for perimenopausal care were evaluated in the dorsal lithotomy position for pelvic prolapse at enrollment and again at 12 months. Prolapse was scored according to the Pelvic Organ Prolapse staging system, as approved by the International Continence Society. All subjects completed questionnaires to obtain demographic data, reproductive history, and gynecologic history. Data were evaluated with the Mann-Whitney rank sum test and with 1-way analysis of variance on ranks. RESULTS: The subjects had a mean parity of 2.2 and a mean weight of 72.4 kg. Hysterectomy had been performed in 28% of the women. Urinary incontinence was reported by 66% of the women at enrollment. Mean prolapse scores that described the position of the cervix, the position of the posterior fornix, and the total vaginal length were significantly changed by the 1-year follow-up, with scores reflecting increased prolapse. The mean score at point Ba, which represents the proximal portion of the anterior vaginal wall, was significantly lower, consistent with decreased prolapse at this site. History of smoking, prior hysterectomy, weight, parity, and incontinence at enrollment did not significantly correlate with any of the 9 measured prolapse points. CONCLUSIONS: Normative data for the Pelvic Organ Prolapse staging system of the International Continence Society, American Urogynecologic Society, and Society of Gynecologic Surgeons were measured in a group of perimenopausal women. Apparent increases in prolapse at points C, D, and tvl may reflect changes in vaginal size rather an increase in uterine or vaginal vault prolapse. This variability may confound the use of the Pelvic Organ Prolapse staging system in longitudinal studies involving perimenopausal women.

Validity and reproducibility of a food frequency interview in a Multi-Cultural Epidemiology Study.

PURPOSE: There is limited support for the validity and reproducibility of dietary assessment in culturally diverse populations. The goal of this study was to evaluate the comparative validity and reproducibility of a Food Frequency Questionnaire (FFQ) used in the observational, multi-cultural Insulin Resistance Atherosclerosis Study (IRAS). METHODS: Women (n = 186) were approximately equally distributed by ethnicity from one urban center (African Americans and non-Hispanic whites) and one rural center (Hispanics and non-Hispanic whites). The IRAS FFQ was modified from the National Cancer Institute Health Habits and History Questionnaire to include ethnic and regional foods. Validity was assessed by comparing dietary values, including supplements, obtained from the FFQ to the average intake estimated from a series of 8 24-hour dietary recalls collected by telephone over the same 1-year period. Reproducibility was assessed among women who reported no change in their usual diet (n = 133) by comparing data from the original IRAS FFQ (in-person) with the FFQ administered for the validity study (two to four years later, by telephone). RESULTS: Correlation coefficients for validity were statistically significant for most nutrients (mean r = 0.62 urban non-Hispanic white, 0.61 rural non-Hispanic whites, 0.50 African American, 0.41 Hispanic) and did not differ among subgroups of obesity or diabetes status. The median correlation coefficient for the total sample was 0.49. Correlations were lower for women with less than 12 years of education (mean r = 0.30; median r = 0.25). The lower correlations among Hispanics was largely explained by the lower educational attainment in that sample. For reproducibility, the mean correlation for nutrients evaluated was r = 0.62 (median r = 0.63) and did not differ for subgroups. CONCLUSIONS: Although educational attainment must be considered, the IRAS FFQ appears to be reasonably valid and reliable in a diverse cohort.