A missense variant in CREBRF, rs373863828, is associated with fat-free mass, not fat mass in Samoan infants.

BACKGROUND/OBJECTIVES: In Samoa, where 80% of the adult population is living with obesity, understanding the determinants of adiposity and growth during infancy may inform prevention efforts. We examined the association of a missense variant, rs373863828, in the CREBRF gene with body composition in Samoan infants. Adults with one or more copies of the rs373863828 minor allele (A) have higher odds of obesity, based on body-mass index (BMI), but paradoxically decreased odds of diabetes compared to those without the allele. Our study may offer novel insight into the natural history and pathogenesis of this unexpected relationship. SUBJECTS/METHODS: In a prospective study, we measured body composition in early infancy, and at 2- and 4-months of age using anthropometry and dual-energy x-ray absorptiometry (DXA). We genotyped subjects at the CREBRF rs373863828 locus and compared infants with (AA/AG) and without (GG) the variant. In longitudinal analyses, we calculated the absolute change in each outcome from the early infant to the 4-month assessment, adjusting for baseline and other covariates. RESULTS: In cross-sectional analyses, there was no significant difference in infant BMI or fat mass by genotype. After adjusting for covariates, infants with the variant had 4.0 ± 1.8 g more bone mass (p = 0.026) and 210.9 ± 79.6 g more lean mass (p = 0.009) at 4-months and accumulated 176.9 ± 73.0 g more lean mass between the early infant and 4-month assessment (p = 0.017). CONCLUSIONS: The CREBRF rs373863828 minor allele (A) was not associated with increased BMI or adiposity in Samoan infants, but instead with increased lean and bone mass. Our findings suggest that lean (i.e., muscle) and bone mass accretion should be explored as pathways to explain the "protective" effect of the CREBRF variant against diabetes.

Reproductive health, obesity, and cardiometabolic risk factors among Samoan women.

OBJECTIVES: Obesity leads to deleterious effects on not only cardiovascular health but also on the reproductive health of women. We estimate the prevalence of menstrual irregularity and of polycystic ovarian syndrome (PCOS) in Samoan women, among whom obesity prevalence is extremely high. We explore the association of these reproductive health conditions with adiposity, cardiometabolic risk factors, and androgen levels. METHODS: A cross-sectional sample of Samoan women 25-39 years of age (n = 470) from a larger population-based genome-wide association study of adiposity and cardiometabolic disease was assessed for the prevalence of oligomenorrhea/amenorrhea (OM/AM) using a self-reported questionnaire. Serum androgens and anti-Müllerian hormone levels were assayed to determine hyperandrogenemia and presence of polycystic ovaries (PCO), respectively, using criterion values. PCOS was classified using NIH guidelines of having at least two of the three conditions: menstrual irregularity, hyperandrogenism, and PCO. We contrasted socio-demographic, reproductive health, and cardiometabolic risk factors between those with and without OM/AM and similarly for PCOS. RESULTS: The prevalence of OM/AM was 7.4% (95% CI: 5.1, 9.8), and women with OM/AM had significantly higher central adiposity. PCOS was estimated at 6.8% (95% CI: 4.5, 9.1), and those with PCOS were younger but had higher overall and central adiposity measures, higher triglycerides, and higher prevalence of insulin resistance than women without PCOS. CONCLUSIONS: The prevalence of menstrual irregularity and PCOS are less than hypothesized given the high levels of adiposity in this population. Nevertheless, Samoan women with menstrual irregularity and other features of PCOS have significantly poorer metabolic health.

Trends in diabetes and obesity in Samoa over 35 years, 1978-2013.

AIMS: Population surveys of Type 2 diabetes mellitus and obesity conducted in Samoa over three decades have used varying methodologies and definitions. This study standardizes measures, and trends of Type 2 diabetes mellitus and obesity for 1978-2013 are projected to 2020 for adults aged 25-64 years. METHODS: Unit records from eight surveys (n = 12 516) were adjusted to the previous census for Division of residence, sex and age to improve national representativeness. Type 2 diabetes mellitus is defined as a fasting plasma glucose ≥ 7.0 mmol/l and/or on medication. Obesity is defined as BMI ≥ 30 kg/m2 . Random effects meta-regression was employed to assess time trends following logit transformation. Poisson regression from strata was used to assess the effects of mean BMI changes on Type 2 diabetes mellitus period trends. RESULTS: Over 1978-2013, Type 2 diabetes mellitus prevalence increased from 1.2% to 19.6% in men (2.3% per 5 years), and from 2.2% to 19.5% in women (2.2% per 5 years). Obesity prevalence increased from 27.7% to 53.1% in men (3.6% per 5 years) and from 44.4% to 76.7% (4.5% per 5 years) in women. Type 2 diabetes mellitus and obesity prevalences increased in all age groups. From period trends, Type 2 diabetes mellitus prevalence in 2020 is projected to be 26% in men and women. Projected obesity prevalence is projected to be 59% in men and 81% in women. Type 2 diabetes mellitus period trends attributable to BMI increase are estimated as 31% (men) and 16% (women), after adjusting for age. CONCLUSION: This is the first study to produce trends of Type 2 diabetes mellitus and obesity in Samoa based on standardized data from population surveys. Type 2 diabetes mellitus is equally prevalent in both sexes, and obesity is widespread. Type 2 diabetes mellitus prevalence in Samoa is likely to continue to increase in the near future.

Potential effectiveness of Community Health Strategy to promote exclusive breastfeeding in urban poor settings in Nairobi, Kenya: a quasi-experimental study.

Early nutrition is critical for later health and sustainable development. We determined potential effectiveness of the Kenyan Community Health Strategy in promoting exclusive breastfeeding (EBF) in urban poor settings in Nairobi, Kenya. We used a quasi-experimental study design, based on three studies [Pre-intervention (2007-2011; n=5824), Intervention (2012-2015; n=1110) and Comparison (2012-2014; n=487)], which followed mother-child pairs longitudinally to establish EBF rates from 0 to 6 months. The Maternal, Infant and Young Child Nutrition (MIYCN) study was a cluster randomized trial; the control arm (MIYCN-Control) received standard care involving community health workers (CHWs) visits for counselling on antenatal and postnatal care. The intervention arm (MIYCN-Intervention) received standard care and regular MIYCN counselling by trained CHWs. Both groups received MIYCN information materials. We tested differences in EBF rates from 0 to 6 months among four study groups (Pre-intervention, MIYCN-Intervention, MIYCN-Control and Comparison) using a χ(2) test and logistic regression. At 6 months, the prevalence of EBF was 2% in the Pre-intervention group compared with 55% in the MIYCN-Intervention group, 55% in the MIYCN-Control group and 3% in the Comparison group (P<0.05). After adjusting for baseline characteristics, the odds ratio for EBF from birth to 6 months was 66.9 (95% CI 45.4-96.4), 84.3 (95% CI 40.7-174.6) and 3.9 (95% CI 1.8-8.4) for the MIYCN-Intervention, MIYCN-Control and Comparison group, respectively, compared with the Pre-intervention group. There is potential effectiveness of the Kenya national Community Health Strategy in promoting EBF in urban poor settings where health care access is limited.

Schistosoma japonicum in Samar, the Philippines: infection in dogs and rats as a possible risk factor for human infection.

The role that animals play in the transmission of Schistosoma japonicum to humans in the Philippines remains uncertain and prior studies have not included several species, adjustment for misclassification error and clustering, or used a cohort design. A cohort study of 2468 people providing stool samples at 12 months following praziquantel treatment in 50 villages of Western Samar, the Philippines, was conducted. Stool samples from dogs, cats, rats, and water buffaloes were collected at baseline (2003-2004) and follow-up (2005). Latent-class hierarchical Bayesian log-binomial models adjusting for misclassification errors in diagnostic tests were used. The village-level baseline and follow-up prevalences of cat, dog, and rat S. japonicum infection were associated with the 12-month cumulative incidence of human S. japonicum infection, with similar magnitude and precision of effect, but correlation between infection levels made it difficult to divide their respective effects. The cumulative incidence ratios associated with a 1% increase in the prevalence of infection in dogs at baseline and in rats at follow-up were 1·04 [95% Bayesian credible interval (BCI) 1·02-1·07] and 1·02 (95% BCI 1·01-1·04), respectively, when both species were entered in the model. Dogs appear to play a role in human schistosomiasis infection while rats could be used as schistosomiasis sentinels.

The contribution of feeding mode to obesogenic growth trajectories in American Samoan infants.

UNLABELLED: What is already known about this subject Samoan adults are recognized for their particularly high body mass index and prevalent obesity. While Polynesians are understudied, in other populations infancy is a critical period in the development of obesity. Breastfeeding has been shown to attenuate obesity risk. What this study adds Samoan infants show remarkably rapid gain in weight but not length in early infancy resulting in a prevalence of overweight and obesity far higher than has been previously reported elsewhere. Breastfeeding is associated with slower weight gain in infancy suggesting that its protective benefits for obesity risk are generalizable outside of European-derived populations. BACKGROUND: Samoans are recognized for their particularly high body mass index and prevalent adult obesity but infants are understudied. OBJECTIVE: To examine the prevalence of overweight and obesity and determine the contribution of feeding mode to obesogenic growth trajectories in American Samoan infants. METHODS: Data were extracted from the well baby records of 795 (n = 417 male) Samoan infants aged 0-15 months. Mixed-effects growth models were used to produce individual weight and length curves. Further mixed-effects models were fitted with feeding mode (breastfed, formula- or mixed-fed) as a single observation at age 4 (±2) months. Weight and length values were converted to z-scores according to the Centers for Disease Control 2000 reference. RESULTS: At 15 months, 23.3% of boys and 16.7% of girls were obese (weight-for-length > 95th percentile). Feeding mode had a significant effect on weight and length trajectories. Formula-fed infants gained weight and length faster than breastfed infants. Formula-fed boys were significantly more likely to be obese at 15 months (38.6%) than breastfed boys (23.4%), χ(2) = 8.4, P < 0.01, odds ratio = 2.05, 95% confidence interval (1.04, 4.05). CONCLUSION: Obesity in American Samoans is not confined to adults. Obesity prevention efforts should be targeted at early life and promotion of breastfeeding may be a suitable intervention target.

INSIG2 variants, dietary patterns and metabolic risk in Samoa.

BACKGROUND/OBJECTIVES: Association of insulin-induced gene 2 (INSIG2) variants with obesity has been confirmed in several but not all follow-up studies. Differences in environmental factors across populations may mask some genetic associations and therefore gene-environment interactions should be explored. We hypothesized that the association between dietary patterns and components of the metabolic syndrome could be modified by INSIG2 variants. SUBJECTS/METHODS: We conducted a longitudinal study of adiposity and cardiovascular disease risk among 427 and 290 adults from Samoa and American Samoa (1990-1995). Principal component analysis on food items from a validated food frequency questionnaire was used to identify neotraditional and modern dietary patterns. We explored gene-dietary pattern interactions with the INSIG2 variants rs9308762 and rs7566605. RESULTS: Results for American Samoans were mostly nonsignificant. In Samoa, the neotraditional dietary pattern was associated with lower triglycerides, body mass index (BMI), waist circumference, systolic and diastolic blood pressure and fasting glucose (all P-for-trend<0.05). The modern pattern was significantly associated with higher triglycerides, BMI, waist circumference and lower high-density lipoprotein-cholesterol (all P-for-trend<0.05). A significant interaction for triglycerides was found between the modern pattern and the rs9308762 polymorphism (P=0.04). Those from Samoa consuming the modern pattern have higher triglycerides if they are homozygous for the rs9308762 C allele. CONCLUSIONS: The common INSIG2 variant rs9308762 was associated with poorer metabolic control and a greater sensitivity of trigylcerides to a modern dietary pattern. Environmental factors need to be taken into account when assessing genetic associations across and within populations.

First assessment of menstrual cycle function and reproductive endocrine status in Samoan women.

BACKGROUND: American Samoa and Samoa are now characterized by one of the world's highest levels of adult overweight and obesity. Our objective was to investigate patterns of menstrual cyclicity reported by Samoan women and examine the relationship to adiposity and select hormone levels. METHODS: A cross-sectional analysis was performed among Samoan women, aged 18-39 years (n = 322), using anthropometric and biomarker measures of adiposity and reproductive health, including insulin, adiponectin, testosterone, sex hormone-binding globulin, free androgen index (FAI) and mullerian-inhibiting substance (MIS). Menstrual regularity was assessed from self-reported responses. Multivariable models were estimated to adjust for potential confounding of the associations between menstrual patterns and other measures. RESULTS: A high proportion of the women (13.7%) reported oligomenorrhea or amenorrhea (OM/AM). More than three-quarters, 80.7%, of women were either overweight or obese, using Polynesian-specific criteria, and OM/AM was significantly associated with higher BMI. Abdominal circumference and insulin levels were significantly higher, and adiponectin levels were lower, in those who reported OM/AM versus regular menstruation. The FAI was higher in women with increased BMI. MIS levels declined with age, more slowly in those reporting OM/AM. CONCLUSIONS: Self-reported OM/AM was associated with an elevated BMI, abdominal adiposity and serum insulin, and with reduced adiponectin levels. These findings support a high rate of metabolic syndrome, and perhaps PCOS and reproductive dysfunction, among Samoan women.

Estimating the sensitivity and specificity of Kato-Katz stool examination technique for detection of hookworms, Ascaris lumbricoides and Trichuris trichiura infections in humans in the absence of a 'gold standard'.

The accuracy of the Kato-Katz technique in identifying individuals with soil-transmitted helminth (STH) infections is limited by day-to-day variation in helminth egg excretion, confusion with other parasites and the laboratory technicians' experience. We aimed to estimate the sensitivity and specificity of the Kato-Katz technique to detect infection with Ascaris lumbricoides, hookworm and Trichuris trichiura using a Bayesian approach in the absence of a 'gold standard'. Data were obtained from a longitudinal study conducted between January 2004 and December 2005 in Samar Province, the Philippines. Each participant provided between one and three stool samples over consecutive days. Stool samples were examined using the Kato-Katz technique and reported as positive or negative for STHs. In the presence of measurement error, the true status of each individual is considered as latent data. Using a Bayesian method, we calculated marginal posterior densities of sensitivity and specificity parameters from the product of the likelihood function of observed and latent data. A uniform prior distribution was used (beta distribution: alpha=1, beta=1). A total of 5624 individuals provided at least one stool sample. One, two and three stool samples were provided by 1582, 1893 and 2149 individuals, respectively. All STHs showed variation in test results from day to day. Sensitivity estimates of the Kato-Katz technique for one stool sample were 96.9% (95% Bayesian Credible Interval [BCI]: 96.1%, 97.6%), 65.2% (60.0%, 69.8%) and 91.4% (90.5%, 92.3%), for A. lumbricoides, hookworm and T. trichiura, respectively. Specificity estimates for one stool sample were 96.1% (95.5%, 96.7%), 93.8% (92.4%, 95.4%) and 94.4% (93.2%, 95.5%), for A. lumbricoides, hookworm and T. trichiura, respectively. Our results show that the Kato-Katz technique can perform with reasonable accuracy with one day's stool collection for A. lumbricoides and T. trichiura. Low sensitivity of the Kato-Katz for detection of hookworm infection may be related to rapid degeneration of delicate hookworm eggs with time.

A whole genome linkage scan identifies multiple chromosomal regions influencing adiposity-related traits among Samoans.

We conducted a genome-wide scan in 46 pedigrees, with 671 phenotyped adults, from the independent nation of Samoa to map quantitative trait loci (QTLs) for adiposity-related phenotypes, including body mass index (BMI), abdominal circumference (ABDCIR), percent body fat (%BFAT), and fasting serum leptin and adiponectin. A set of 378 autosomal and 14 X chromosomal microsatellite markers were genotyped in 572 of the adults. Significant genetic correlations (0.82-0.96) were detected between pairs of BMI, ABDCIR, %BFAT and leptin. Suggestive linkages were found on 13q31 (LOD = 2.30 for leptin, LOD = 2.48 for %BFAT, LOD = 2.04 for ABDCIR, and LOD = 2.09 for BMI) and on 9p22 (LOD = 3.08 for ABDCIR and LOD = 2.53 for %BFAT). Furthermore, bivariate linkage analyses indicated that the genetic regions on 9p22 (bivariate LOD 2.35-3.10, LOD(eq) (1df) 1.88-2.59) and 13q31 (bivariate LOD 1.96-2.64, LOD(eq) 1.52-2.21) might harbor common major genes with pleiotropic effects. Other regions showing suggestive linkage included 4q22 (LOD = 2.95) and 7p14 (LOD = 2.64) for %BFAT, 2q13 for adiponectin (LOD = 2.05) and 19q12 for BMI-adjusted leptin (LOD = 2.03). Further fine mapping of these regions may help identify the genetic variants contributing to the development of obesity in Samoan adults.

Genome-wide scan for adiposity-related phenotypes in adults from American Samoa.

OBJECTIVE: To detect quantitative trait loci influencing adiposity-related phenotypes assessed by body mass index (BMI), abdominal circumference (ABDCIR), percent body fat (%BFAT) and fasting serum leptin and adiponectin using a whole genome linkage scan of families from American Samoa. DESIGN: Family-based linkage analysis, the probands and family members were unselected for obesity. SUBJECTS: A total of 583 phenotyped American Samoan adults, of which 578 were genotyped in 34 pedigrees. MEASUREMENTS: A total of 377 autosomal and 18 X chromosome microsatellite markers were typed at an approximate average spacing of 10 cM spanning the genome. Multipoint LOD (logarithm of the odds) scores were calculated using variance-components approaches and SOLAR/LOKI software. The covariates simultaneously evaluated were age, sex, education, farm work and cigarette smoking, with a significance level of 0.1. Due to the stochastic nature of LOKI, we report the average of maximum LOD scores from 10 runs. RESULTS: Significant linkage to leptin was found at 6q32.2 with LOD of 3.83. Suggestive linkage to leptin was found at 16q21:LOD=2.98, 1q42.2:LOD=1.97, 5q11.2:LOD=2.08, 12q24.23:LOD=2.00, 19p13.3:LOD=2.05; adiponectin was linked to 13q33.1-q22.1:LOD=2.41; %BFAT was linked to 16q12.2-q21, LOD=2.24; ABDCIR was linked to 16q23.1:LOD=1.95; %BFAT-adjusted leptin to 14q12, LOD=2.01; %BFAT-adjusted ABDCIR to 1q31.1, LOD=2.36, to 3q27.3-q28, LOD=2.10 and to 12p12.3, LOD=2.04. CONCLUSION: We found strong evidence for a major locus on 6q23.2 influencing serum leptin levels in American Samoans. The 16q21 region appears to harbor a susceptibility locus that has significant pleiotrophic effects on phenotypes BMI, %BFAT, leptin and ABDCIR as shown by bivariate linkage analyses. Several other loci of varying significance were detected across the genome.

Prevalence of Schistosoma japonicum infection among animals in fifty villages of Samar province, the Philippines.

In the Philippines, there is a need to understand the contribution of different domestic and wild animals in transmitting Schistosoma japonicum infection to humans better. The current study describes variation in animal S. japonicum prevalence across 50 endemic villages of Samar Province, the Philippines. A total of 50 villages were selected, 25 with predominantly rain-fed farms and 25 with some irrigation system. At least 35 cats, dogs, pigs, and water buffaloes each were randomly selected and 30 rat traps were set in each village. Fecal samples were collected for up to three consecutive days for each species. The Danish Bilharziasis Laboratory method (DBL method) was used to determine S. japonicum infection status. A hierarchical logistic regression model with clustering by village and with adjustment for measurement error of the DBL method was used to estimate the prevalence of infection per village and species. Stool samples were collected from 23.4% (1189), 28.6% (1274), 36.3% (1899), and 49.4% (873) of the censused dogs, cats, pigs, and water buffaloes, respectively, and from 663 rats. The adjusted prevalence of S. japonicum infection varied greatly across villages ranging from 1.6% (95% Bayesian Credible Interval: 0.1%-10.2%) to 86.3% (65.9%-97.8%) for dogs, from 0.1% (0%-2.1%) to 21.7% (4.7%-51.2%) for cats, from 0.01% (0.0%%-1.0%) to 18.4% (7.1%-34.7%) for pigs, from less than 0.1% (0.0%-1.2%) to 72.5% (46.0%-97.4%) for water buffaloes, and from 0.7% (0.0%-9.0%) to 95.4% (77.2%-99.9%) for rats. This is the most comprehensive study of animal S. japonicum infection conducted to date. Our results show that, unlike what has been reported in China, very few water buffaloes were infected whereas rats and dogs show high prevalence proportions of infection. This, combined with significant village-to-village variation in prevalence of S. japonicum infection, suggest possible different transmission dynamics of the infection in the Province of Samar in the Philippines and China.

Th2 cytokines are associated with persistent hepatic fibrosis in human Schistosoma japonicum infection.

We conducted a prospective cohort study in Leyte, the Philippines, among 611 Schistosoma japonicum-infected participants 7-30 years old, all of whom were treated with praziquantel at baseline. To detect hepatic fibrosis, abdominal ultrasound was performed at baseline and 12 months after treatment. Stool for assessment of S. japonicum infection was collected at baseline and at 3, 6, 9, and 12 months after treatment. Cytokines (interleukin [IL]-4, IL-5, IL-10, IL-13, tumor necrosis factor- alpha , and interferon- gamma ) produced by peripheral-blood mononuclear cells in response to soluble worm antigen preparation (SWAP), soluble egg antigen (SEA), and control medium were measured once 4 weeks after treatment. IL-4 to SWAP and IL-10 to both SWAP and SEA were associated with the presence of baseline fibrosis after adjustment for potential confounding variables (P<.03, for all). In participants with fibrosis at baseline, IL-4 to SWAP and IL-5 and IL-13 to both SWAP and SEA were associated with persistent fibrosis at 12 months after treatment (P<.05, for all). Males showed consistently stronger T helper 2 (Th2) cytokine responses to both SWAP and SEA than did females (P<.02, for all). These results suggest an independent role for Th2-biased cytokine responses to S. japonicum antigens in persistent hepatic fibrosis and indicate that Th2 cytokines may contribute to the male-biased prevalence of fibrosis.

Protective immunity induced by phage displayed mitochondrial related peptides of Schistosoma japonicum.

New antigens and strategies are necessary for vaccine development against schistosomiasis japonica. Using a pool of 43 high titred anti-SWA sera from individuals residing in an Schistosoma japonicum endemic area of China, we have cloned a S. japonicum gene by cDNA library screening. The recombinant Sj338 protein has 44-46% identity to a mitochondrial precursor receptor protein of humans and rats. Immunization of mice with the recombinant Sj338 conferred 27-32% (p<0.01) reduction in worm burdens following cercarial challenge. In an effort to identify protective epitopes in Sj338 and increase the level of protection, we screened a random 12-mer peptide library constructed in M13 using a polyspecific anti-Sj338 rabbit serum. After five rounds of biopanning, we identified 30 reactive clones consisting of 11 distinct peptide sequences. These clones shared limited primary sequence homology with the recombinant Sj338 protein. Anti-sera raised against these phage clones recognized recombinant Sj338 and SWAP by Western blot. In murine vaccination experiments using whole recombinant phage without adjuvant, four of these clones demonstrated worm reductions of 11.6-25.1% (p=ns - 0.05) compared to M13 vaccinated animals. Animals vaccinated with all four of these phage demonstrated 34.2% (p<0.01) worm reduction compared to controls vaccinated with M13 clone. These data suggest that mimotope peptides are potential vaccine candidates for S. japonicum.

Concurrent comparison of three water contact measurement tools in four endemic villages of the Philippines. The schistosomiasis transmission ecology in the Philippines project (STEP).

BACKGROUND: Schistosomiasis japonica is a chronic helminthic infection contracted through contact with water infested with Schistosoma japonicum. The infection is associated with severe disease and is an important public health concern in Philippines. OBJECT: To estimate the agreement in the frequency of water contact between bimonthly interviews, self-administered diaries and observations. METHODS: A total of 286 individuals were followed over either a 4 or a 6 months period. Agreement between direct observation and both the bimonthly and diary methods were estimated. RESULTS: The agreement between the observation and the bimonthly interview was 71.8% when days without any water contacts were considered, but decreased to 23.3% when only days with at least some water contact were considered. The agreement between the observation and the diary was 78.7% when days without any water contacts were considered and 40.8% when only days with some water contacts were considered. CONCLUSIONS: Agreement about the degree of water contact is poor between the different measurement tools. This has important implications for future research, since a high degree of measurement error can severely bias any results from studies involving water contact.

Estimating sensitivity and specificity of a faecal examination method for Schistosoma japonicum infection in cats, dogs, water buffaloes, pigs, and rats in Western Samar and Sorsogon Provinces, The Philippines.

Schistosoma japonicum causes a chronic parasitic disease, which persists as a major public health concern in The Philippines, the People's Republic of China and Indonesia. This infection is unique among helminthic zoonoses because it can infect humans and more than 40 other mammals. The objective of this study was to estimate the sensitivity and specificity of the Danish Bilharziasis Laboratory technique in cats, dogs, pigs, water buffaloes and rats in the Philippines. Faecal samples from each animal were collected on up to five occasions on five consecutive days in four villages of Sorsogon and Western Samar Provinces between January and July 2003. The faecal samples were analysed with the filtration and sedimentation Danish Bilharziasis Laboratory technique. Sensitivity and specificity of one, two, three, four, and five faecal samples were estimated using a Bayesian latent class approach. A total of 59, 43, 74, and 80% of the censored cats, dogs, pigs, and water buffaloes in the four villages were sampled, respectively. For all species, the sensitivity estimates when using the results of only 1 day of sampling were less than 80%. However, the sensitivity improved to at least 96% in all species when three or more faecal samples were collected on three separate days. The specificity was estimated to be above 92% across all species, even if just a single sample is used. The prevalences and 95% credible intervals of S. japonicum, adjusted for imperfect sensitivity and specificity, in cats, dogs, pigs, rats, and water buffaloes were 11.9% (6.8-18.3%), 19.9% (15.1-25.2%), 2.9% (1.1-5.2%), 31.3% (18.3-45.6%) and 6.3% (2.1-12.6%), respectively. Our results suggest that the Danish Bilharziasis Laboratory technique is valid for the detection of infection with S. japonicum in animals, and that sensitivity estimates are excellent when faecal samples are collected on at least three different days. Monitoring S. japonicum infection in animal reservoirs with a valid test could contribute to more effective public health control programmes.

Human leptin locus (LEP) alleles and BMI in Samoans.

OBJECTIVES: Because of their location in known candidate gene regions for obesity the associations between six microsatellite markers (D2S2170, D2S144, D2S1268, D2S1788, D2S1348 and a tetranucleotide repeat in the 3' UTR of the LEP locus) and body mass index (BMI) were studied in adult Samoans. DESIGN: The study was designed to detect differences in the proportion of alleles at the six microsatellite markers between two groups of adult Samoans at the extremes of the longitudinal BMI distribution. SUBJECTS AND MEASUREMENTS: The 181 unrelated Samoan participants were 25-55 y of age, reported that all four grandparents were Samoan, resided in American Samoa (AS) or Samoa (S) and were without diagnosed hypertension or type 2 diabetes. Initial statistical analysis was based on chi(2) tests of independence between marker allele frequencies and BMI status at each marker. The association of individual alleles with BMI status was tested by aggregating a marker's allelic data into a two-by-two contingency table and applying a two-tailed version of Fisher's exact test, with a Bonferroni correction to account for the multiple testing implicit in the procedure. RESULTS: There were no significant differences in allele frequencies at any of the markers between AS and S, as expected from our prior population genetic analyses. Only the LEP gene 3'-tetranucelotide repeat was associated (P<0.006) with BMI status. The distribution of the marker alleles at the LEP locus was significantly associated with the BMI groups (P<0.01), due to the low frequency of allele 226 in the high BMI group. The same pattern of association was found in sub-group analyses with low BMI individuals from AS and high BMI individuals from S. CONCLUSION: These findings indicate that the leptin 3'-tetranucleotide repeat is associated with high BMI in adult Samoans, with allele 226 having a low frequency in the high BMI group.

Type 2 diabetes and three calpain-10 gene polymorphisms in Samoans: no evidence of association.

Although genomewide scans have identified several potential chromosomal susceptibility regions in several human populations, finding a causative gene for type 2 diabetes has remained elusive. Others have reported a novel gene, calpain-10 (CAPN10), located in a previously identified region on chromosome 2q37.3, as a putative susceptibility gene for type 2 diabetes. Three single-nucleotide polymorphisms (SNPs) (UCSNP43, UCSNP19, and UCSNP63) were shown to be involved in increased risk of the disease among Mexican Americans. We have tested the association of these three SNPs with type 2 diabetes among the Samoans of Polynesia, who have a very high prevalence of the disease. In the U.S. territory of American Samoa, prevalence is 25% and 15% in men and women, respectively, whereas, in the independent nation of Samoa, prevalence is 3% and 5% in men and women, respectively. In our study sample, which consisted of 172 unrelated affected case subjects and 96 control subjects, we failed to detect any association between case subjects and control subjects in allele frequencies, haplotype frequencies, or haplotype combinations of UCSNP43, -19, and -63. Also, our data showed no evidence of linkage, among 201 affected sib pairs, in the region of chromosome 2 that contains these SNPs. Three plausible scenarios could explain these observations. (1) CAPN10 is a susceptibility gene only in particular ethnic groups; (2) our study lacks power to detect the effects of CAPN10 polymorphisms (but our sample size is comparable to that of earlier reports); or (3) the underlying biological mechanism is too complex and requires further research.

Genetic and environmental correlations between various anthropometric and blood pressure traits among adult Samoans.

Shared polygenic effects (i.e., pleiotropy) are assumed to exist for such obesity-related phenotypes as blood pressure and adiposity. It is possible to identify these shared genetic effects through bivariate genetic analyses. This analysis of 1,342 adult Samoans, across 801 pedigrees, indicates that significant heritable components (P < 0.05) ranging from 29-58% exist for weight, height, systolic blood pressure, diastolic blood pressure, triceps skinfold, subscapular skinfold, body mass index, and sum of skinfolds. In general, the anthropometric measurements share additive genetic effects, as do the anthropometric measures, with blood pressure. Heritabilities for central fat distribution are not significant in this population, which could be due to a lack of power. On the other hand, heritabilities have been found in Hispanics; hence the genes responsible for central fat distribution may not be evenly distributed among populations.

Genetic effect of two APOA repeat polymorphisms (kringle 4 and pentanucleotide repeats) on plasma Lp(a) levels in American Samoans.

Elevated plasma lipoprotein(a) [Lp(a)] level has been established as an independent risk factor for atherosclerosis and coronary heart disease. Considerable ethnic group differences in the distribution of plasma Lp(a) levels have raised public health concerns. Recently, we have reported that Samoans have the lowest plasma Lp(a) levels of any population group. In the present investigation, we report the contribution of two apolipoprotein(a) (APOA) polymorphisms, the kringle 4 type 2 (K4) repeat and the pentanucleotide repeat (PNR), in affecting plasma Lp(a) levels in an American Samoan sample (n = 309). The K4 repeats ranged in size from 15 to 40. The common alleles contained repeats ranging from 26 to 36 with allele frequencies between 5.5% to 9.7%, and these accounted for 82% of all alleles. An inverse relationship between K4 repeat number and plasma Lp(a) level was observed for single-banded (r = -0.59, p = 0.0001) and double-banded phenotypes (r = -0.50, p = 0.0001). This polymorphism explained 60% of the variation in plasma Lp(a) level in American Samoans. For the PNR polymorphism, five different repeat alleles and eight different genotypes were identified; the most common allele was eight repeats. The *8 PNR allele was associated with a wide range of K4 repeats, the *9 PNR allele with larger K4 repeats (25-40), and the *10 PNR with smaller K4 repeats (15-24). Analysis of variance (ANOVA) revealed that the PNR polymorphism accounts for 2.1% of the variability in plasma Lp(a) levels in this sample, when the K4 repeat polymorphism was taken into account. Our data show that common polymorphisms in the APOA gene are major determinants of plasma Lp(a) variation in American Samoans.