The tumour-derived extracellular vesicle proteome varies by endometrial cancer histology and is confounded by an obesogenic environment.

Endometrial cancer, the most common gynaecological cancer worldwide, is closely linked to obesity and metabolic diseases, particularly in younger women. New circulating biomarkers have the potential to improve diagnosis and treatment selections, which could significantly improve outcomes. Our approach focuses on extracellular vesicle (EV) biomarker discovery by directly profiling the proteome of EVs enriched from frozen biobanked endometrial tumours. We analysed nine tissue samples to compare three clinical subgroups-low BMI (Body Mass Index) Endometrioid, high BMI Endometrioid, and Serous (any BMI)-identifying proteins related to histological subtype, BMI, and shared secreted proteins. Using collagenase digestion and size exclusion chromatography, we successfully enriched generous quantities of EVs (range 204.8-1291.0 µg protein: 1.38 × 1011-1.10 × 1012 particles), characterised by their size (∼150 nm), expression of EV markers (CD63/81), and proposed endometrial cancer markers (L1CAM, ANXA2). Mass spectrometry-based proteomic profiling identified 2075 proteins present in at least one of the 18 samples. Compared to cell lysates, EVs were successfully depleted for mitochondrial and blood proteins and enriched for common EV markers and large secreted proteins. Further analysis highlighted significant differences in EV protein profiles between the high BMI subgroup and others, underlining the impact of comorbidities on the EV secretome. Interestingly, proteins differentially abundant in tissue subgroups were largely not also differential in matched EVs. This research identified secreted proteins known to be involved in endometrial cancer pathophysiology and proposed novel diagnostic biomarkers (EIF6, MUC16, PROM1, SLC26A2).

Liposome-enabled bufalin and doxorubicin combination therapy for trastuzumab-resistant breast cancer with a focus on cancer stem cells.

Breast cancer stem cells (BCSCs) play a key role in therapeutic resistance in breast cancer treatments and disease recurrence. This study aimed to develop a combination therapy loaded with pH-sensitive liposomes to kill both BCSCs and the okbulk cancer cells using trastuzumab-sensitive and resistant human epidermal growth factor receptor 2 positive (HER2+) breast cancer cell models. The anti-BCSCs effect and cytotoxicity of all-trans retinoic acid, salinomycin, and bufalin alone or in combination with doxorubicin were compared in HER2+ cell line BT-474 and a validated trastuzumab-resistant cell line, BT-474R. The most potent anti-BCSC agent was selected and loaded into a pH-sensitive liposome system. The effects of the liposomal combination on BCSCs and bulk cancer cells were assessed. Compared with BT-474, the aldehyde dehydrogenase positive BCSC population was elevated in BT-474R (3.9 vs. 23.1%). Bufalin was the most potent agent and suppressed tumorigenesis of BCSCs by ∼50%, and showed strong synergism with doxorubicin in both BT-474 and BT-474R cell lines. The liposomal combination of bufalin and doxorubicin significantly reduced the BCSC population size by 85%, and inhibited both tumorigenesis and self-renewal, although it had little effect on the migration and invasiveness. The cytotoxicity against the bulk cancer cells was also enhanced by the liposomal combination than either formulation alone in both cell lines (p < 0.001). The liposomal bufalin and doxorubicin combination therapy may effectively target both BCSCs and bulk cancer cells for a better outcome in trastuzumab-resistant HER2+ breast cancer.

The Role of Lifestyle and Dietary Factors in the Development of Premature Ovarian Insufficiency.

Premature ovarian insufficiency (POI) is a condition that arises from dysfunction or early depletion of the ovarian follicle pool accompanied by an earlier-than-normal loss of fertility in young women. Oxidative stress has been suggested as an important factor in the decline of fertility in women and POI. In this review, we discuss the mechanisms of oxidative stress implicated in ovarian ageing and dysfunction in relation to POI, in particular mitochondrial dysfunction, apoptosis and inflammation. Genetic defects, autoimmunity and chemotherapy, are some of the reviewed hallmarks of POI that can lead to increased oxidative stress. Additionally, we highlight lifestyle factors, including diet, low energy availability and BMI, that can increase the risk of POI. The final section of this review discusses dietary factors associated with POI, including consumption of oily fish, mitochondria nutrient therapy, melatonin, dairy and vitamins that can be targeted as potential interventions, especially for at-risk women and in combination with personalised nutrition. Understanding the impact of lifestyle and its implications for POI and oxidative stress holds great promise in reducing the burden of this condition.

Genetic discrimination by insurance companies in Aotearoa New Zealand: experiences and views of health professionals.

AIMS: Genetic discrimination in insurance is a significant clinical, research and consumer issue. Recently, the Australian life insurance industry introduced a partial moratorium on the use of genetic test results. However, in Aotearoa New Zealand, both life and health insurers can still use genetic results legally to discriminate against applicants. We aimed to document experiences and concerns of New Zealand-based health professionals (HPs) around the potential misuse of genetic test results for insurance purposes. METHODS: We administered an online survey to New Zealand HPs who discuss genetic testing with patients, their experiences regarding the use of genetic test results in insurance and views on regulation. RESULTS: Twenty-three New Zealand HPs responded, 15 of whom worked in genetics clinics, representing >60% of the total New Zealand clinical genetics workforce. Eleven respondents reported having patients who experienced adverse outcomes related to insurance based on genetic results. Respondents reported patients sometimes/often delayed (n=11) or refused (n=4) genetic testing due to insurance concerns. Over 80% of those who answered (n=17/21) believe insurers' use of genetic results should be legally regulated. CONCLUSION: New Zealand HPs have concerns about insurance companies using genetic test results in underwriting, including the effect on patients, and strongly believe government legislation is required.

Stability of trastuzumab during nanomedicine formulation using SEC-HPLC coupled with polyacrylamide gel electrophoresis.

The anti-HER2 antibody trastuzumab has been proven to be an effective targeting ligand for drug delivery. This study investigates the structural integrity of trastuzumab under different stress factors in formulation development and its long-term stability. A validated size exclusion high performance liquid chromatographic (SEC-HPLC) method was first developed. The stability of trastuzumab (0.21-21 mg/ml) under stress conditions (mechanical, freeze-and-thaw, pH and temperature) and long-term storage in the presence of formulation excipients were monitored for up to 12 months, using both the SEC-HPLC method and sodium-dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The anti-proliferation activity of the reconstituted antibody stored at 4 °C against HER2+ BT-474 breast cells was also monitored over 12 months. The developed SEC-HPLC method was sensitive and accurate. Solutions of trastuzumab were resistant to mechanical stress and repeated freeze-and-thaw; but were unstable under acidic (pH 2.0 and 4.0) and alkaline (pH 10.0 and 12.0) environments. The samples degraded over 5 days at 60 °C, and within 24 h at 75 °C. Low temperature (-80 °C or 4 °C) and low concentration (0.21 mg/ml) favoured the long-term stability. The anti-proliferation activity was conserved at 4 °C for at least 12 months. This study provided valuable stability information in developing trastuzumab involved nano-formulation as well as in clinical settings.

Genomic discrimination in New Zealand health and life insurance. AGenDA: Against Genomic Discrimination in Aotearoa.

Nil.

Dual or multiple drug loaded nanoparticles to target breast cancer stem cells.

Breast cancer stem(-like) cells (BCSCs) have been found to be responsible for therapeutic resistance and disease relapse. BCSCs are difficult to eradicate due to their high resistance to conventional treatments and high plasticity. Functionalised nanoparticles have been investigated as smart vehicles to transport across various barriers and increase the interaction of therapeutic agents with cancer cells, as well as BCSCs. In this review, we discuss the different characteristics of BCSCs, and challenges to tackle BCSCs at cellular and molecular levels. The mechanisms of action and physicochemical properties of the current BCSC targeting agents are also covered. We will focus on the rational design and recent advances of "Nano + Nano" or single tumour targeting nanoparticle systems loaded with dual or multiple agents to kill all cancer cells including BCSCs. These cocktail therapies include the combination of a chemotherapy agent with a BCSC-specific inhibitor, a phytochemical agent or RNA based therapy. Given the heterogeneity of breast tumour tissue, targeting both BCSCs and bulk breast cancer cells simultaneously with multiple agents holds great promise in eliminating breast cancer. The future research needs to focus on overcoming various barriers in the 'clinical translation' of BCSC-targeting nanomedicines to cure breast cancer, which requires a significant multidisciplinary effort.

A Predictor of Early Disease Recurrence in Patients With Breast Cancer Using a Cell-free RNA and Protein Liquid Biopsy.

INTRODUCTION: Circulating biomarkers have been increasingly used in the clinical management of breast cancer. The present study evaluated whether RNAs and a protein present in the plasma of patients with breast cancer might have utility as prognostic biomarkers complementary to existing clinical tests. PATIENTS AND METHODS: We performed microarray profiling of small noncoding RNAs in plasma samples from 30 patients with breast cancer and 10 control individuals. Two small noncoding RNAs, including microRNA (miR)-923, were selected and quantified in plasma samples from an evaluation cohort of 253 patients with breast cancer, using droplet digital polymerase chain reaction. We also measured cancer antigen (CA) 15-3 protein levels in these samples. Cox regression survival analysis was used to determine which markers were associated with patient prognosis. RESULTS: As independent markers of prognosis, the plasma levels of miR-923 and CA 15-3 at the time of surgery for breast cancer were significantly associated with prognosis, irrespective of treatment (Cox proportional hazards, P = 3.9 × 10-3 and 1.9 × 10-9, respectively). After building a multivariable model with standard clinical and pathological features, the addition of miR-923 and CA 15-3 information into the model resulted in a significantly better predictor of disease recurrence in patients, irrespective of treatment, compared with the use of clinicopathological data alone (area under the curve at 3 years, 0.858 vs. 0.770 with clinicopathological markers only; P = .017). CONCLUSION: We propose that the plasma levels of miR-923 and CA 15-3, combined with standard clinicopathological predictors, could be used as a preoperative, noninvasive estimate of patient prognosis to identify which women might need more aggressive treatment or closer surveillance after surgery for breast cancer.

Relationships of maternal body mass index and plasma biomarkers with childhood body mass index and adiposity at 6 years: The Children of SCOPE study.

BACKGROUND: Maternal obesity has been implicated in the origins of childhood obesity through a suboptimal environment in-utero. OBJECTIVE: We examined relationships of maternal early pregnancy body mass index (BMI), overweight/obesity, and plasma biomarkers of obesity, inflammation, insulin resistance, and placental function with measures of childhood BMI and adiposity. METHODS: BMI z-score, sum of skinfold thicknesses (SST), body fat percentage (BFP, by bioelectrical impedance), and waist, arm, and hip circumferences were measured in 1173 6-year-old children of nulliparous pregnant women in the Screening for Pregnancy Endpoints (SCOPE) study, New Zealand. Relationships of maternal early pregnancy (15 weeks' gestation) BMI and biomarkers with these childhood anthropometric measures were assessed by linear regression, with appropriate adjustment. RESULTS: 28.1% of mothers were classified as overweight and 10.1% with obesity; compared with normal weight mothers, the BFP of their children were 5.3% higher (0.16 SD [95% CI, 0.04-0.29] p = .01) and 7.8% higher (0.27 [0.08-0.47] p = .006) with comparable values for BMI z-score and arm, waist, and hip circumferences. Early pregnancy maternal BMI and plasma placental growth factor (PlGF) were associated with higher child's SST, BMI z-score, hip circumference, and BFP. None of the metabolic or inflammatory maternal biomarkers were associated with childhood obesity. CONCLUSION: In this contemporary large prospective cohort study with extensive maternal/childhood phenotyping and a high prevalence of maternal overweight/obesity, we found independent relationships of maternal early pregnancy BMI with childhood BMI and adiposity; similar associations were observed with PlGF, which may imply a role for placenta function in the developmental programming of childhood obesity risk.

Human Sensory LTP Predicts Memory Performance and Is Modulated by the BDNF Val66Met Polymorphism.

Background: Long-term potentiation (LTP) is recognised as a core neuronal process underlying long-term memory. However, a direct relationship between LTP and human memory performance is yet to be demonstrated. The first aim of the current study was thus to assess the relationship between LTP and human long-term memory performance. With this also comes an opportunity to explore factors thought to mediate the relationship between LTP and long-term memory. The second aim of the current study was to explore the relationship between LTP and memory in groups differing with respect to brain-derived neurotrophic factor (BDNF) Val66Met; a single-nucleotide polymorphism (SNP) implicated in memory function. Methods: Participants were split into three genotype groups (Val/Val, Val/Met, Met/Met) and were presented with both an EEG paradigm for inducing LTP-like enhancements of the visually-evoked response, and a test of visual memory. Results: The magnitude of LTP 40 min after induction was predictive of long-term memory performance. Additionally, the BDNF Met allele was associated with both reduced LTP and reduced memory performance. Conclusions: The current study not only presents the first evidence for a relationship between sensory LTP and human memory performance, but also demonstrates how targeting this relationship can provide insight into factors implicated in variation in human memory performance. It is anticipated that this will be of utility to future clinical studies of disrupted memory function.

Genomic medicine must reduce, not compound, health inequities: the case for hauora-enhancing genomic resources for New Zealand.

Precision medicine seeks to draw on data from both individuals and populations across disparate domains to influence and support diagnosis, management and prevention in healthcare at the level of the individual patient and their family/whanau. Central to this initiative is incorporating the effects of the inherent variation that lies within genomes and can influence health outcomes. Identifying and interpreting such variation requires an accurate, valid and representative dataset to firstly define what variants are present and then assess the potential relevance for the health of a person, their family/whanau and the wider community to which they belong. Globally the variation embedded within genomes differs enormously and has been shaped by the size, constitution, historical origins and evolutionary history of their source populations. Maori, and more broadly Pacific peoples, differ substantially in terms of genomic variation compared to the more closely studied European and Asian populations. In the absence of accurate genomic information from Maori and Pacific populations, the precise interpretation of genomic data and the success and benefits of genomic medicine will be disproportionately less for those Maori and Pacific peoples. In this viewpoint article we, as a group of healthcare professionals, researchers and scientists, present a case for assembling genomic resources that catalogue the characteristics of the genomes of New Zealanders, with an emphasis on peoples of Maori and Polynesian ancestry, as a healthcare imperative. In proposing the creation of these resources, we note that their governance and management must be led by iwi and Maori and Pacific representatives. Assembling a genomic resource must be informed by cultural concepts and values most especially understanding that, at a physical and spiritual level, whakapapa is embodied within the DNA of a person. Therefore DNA and genomic data that connects to whakapapa (genealogy) is considered a taonga (something precious and significant), and its storage, utilisation and interpretation is a culturally significant activity. Furthermore, such resources are not proposed to primarily enable comparisons between those with Maori and broader Pacific ancestries and other Aotearoa peoples but to place an understanding of the genetic contributors to their health outcomes in a valid context. Ongoing oversight and governance of such taonga by Maori and Pacific representatives will maximise hauora (health) while also minimising the risk of misuse of this information.

The futility of fertility research? Barriers to embryo research in New Zealand.

AIMS: Successive New Zealand Health Ministers have failed to approve guidelines for research using viable human embryos, which effectively places a blanket ban on all research that "uses" viable human embryos in this country. This includes research that aims to improve currently available reproductive technologies, illustrated by a failed application to ministerial ethics committees for a clinical research project investigating the efficacy of in vitro fertilisation procedures. However, no data currently exists describing the degree to which these restrictions are inhibiting reproductive research in this country. METHODS: We have conducted a qualitative survey of New Zealand researchers from 20 major academic, clinical and governmental institutes to qualify the impact these restrictions are having on New Zealand's research outputs. RESULTS: The results suggest dissatisfaction with the current guidelines, and the lack of guidance from the Ministry of Health and associated ethics committees regarding what constitutes embryo research and therefore what research can be performed. CONCLUSIONS: The lack of current guidelines regarding the use of embryos for research is restricting improvements to established reproductive technologies, and any future research. We suggest that the Minister of Health instructs ministerial advisory and ethics committees to review the current guidelines and to define the term "use of embryos".

Discordant association of the CREBRF rs373863828 A allele with increased BMI and protection from type 2 diabetes in Maori and Pacific (Polynesian) people living in Aotearoa/New Zealand.

AIMS/HYPOTHESIS: The A (minor) allele of CREBRF rs373863828 has been associated with increased BMI and reduced risk of type 2 diabetes in the Samoan populations of Samoa and American Samoa. Our aim was to test rs373863828 for associations with BMI and the odds of type 2 diabetes, gout and chronic kidney disease (CKD) in Maori and Pacific (Polynesian) people living in Aotearoa/New Zealand. METHODS: Linear and logistic regression models were used to analyse the association of the A allele of CREBRF rs373863828 with BMI, log-transformed BMI, waist circumference, type 2 diabetes, gout and CKD in 2286 adults. The primary analyses were adjusted for age, sex, the first four genome-wide principal components and (where appropriate) BMI, waist circumference and type 2 diabetes. The primary analysis was conducted in ancestrally defined groups and association effects were combined using meta-analysis. RESULTS: For the A allele of rs373863828, the effect size was 0.038 (95% CI 0.022, 0.055, p = 4.8 × 10-6) for log-transformed BMI, with OR 0.59 (95% CI 0.47, 0.73, p = 1.9 × 10-6) for type 2 diabetes. There was no evidence for an association of genotype with variance in BMI (p = 0.13), and nor was there evidence for associations with serum urate (ß = 0.012 mmol/l, pcorrected = 0.10), gout (OR 1.00, p = 0.98) or CKD (OR 0.91, p = 0.59). CONCLUSIONS/INTERPRETATION: Our results in New Zealand Polynesian adults replicate, with very similar effect sizes, the association of the A allele of rs373863828 with higher BMI but lower odds of type 2 diabetes among Samoan adults living in Samoa and American Samoa.

Gene-by-Activity Interactions on Obesity Traits of 6-Year-Old New Zealand European Children: A Children of SCOPE Study.

PURPOSE: The decline of physical activity in children is considered an important determinant to explain the rising rates of obesity. However, this risk may be augmented in children who are genetically susceptible to increased weight gain. We hypothesized that a sedentary lifestyle and moderate activity will interact with genetic loci, resulting in differential effects in relation to obesity risk. METHODS: We recruited 643 European children born to participants in the New Zealand-based Screening for Pregnancy Endpoints (SCOPE) study. Seventy gene variants were evaluated by the Sequenom assay. Interaction analyses were performed between the genetic variants and the activity type derived from actigraphy, in relation to percentage body fat. RESULTS: We found a statistically significant association between increased proportions of sedentary activity with increased percentage body fat scores (P = .012). The OLFM4-9568856 (P = .01) and GNPDA2-rs10938397 (P = .044) gene variants showed genotype differences with proportions of sedentary activity. Similarly, the OLFM4-9568856 (P = .021), CLOCK-rs4864548 (P = .029), and LEPR-1045895 (P = .047) showed genotype differences with proportions of moderate activity. We found evidence for unadjusted gene-by-activity interactions of SPACA3/SPRASA-rs16967845, PFKP-rs6602024, and SH2B1-rs7498665 on percentage body fat scores. CONCLUSIONS: These findings indicate a differential effect of physical activity in relation to obesity risk, suggesting that children genetically predisposed to increased weight gain may benefit from higher levels of moderate activity.

Gene expression profiling of breast tumours from New Zealand patients.

AIMS: New Zealand has one of the highest rates of breast cancer incidence in the world. We investigated the gene expression profiles of breast tumours from New Zealand patients, compared them to gene expression profiles of international breast cancer cohorts and identified any associations between altered gene expression and the clinicopathological features of the tumours. METHODS: Affymetrix microarrays were used to measure the gene expression profiles of 106 breast tumours from New Zealand patients. Gene expression data from six international breast cancer cohorts were collated, and all the gene expression data were analysed using standard bioinformatic and statistical tools. RESULTS: Gene expression profiles associated with tumour ER and ERBB2 status, molecular subtype and selected gene expression signatures within the New Zealand cohort were consistent with those found in international cohorts. Significant differences in clinicopathological features such as tumour grade, tumour size and lymph node status were also observed between the New Zealand and international cohorts. CONCLUSIONS: Gene expression profiles, which are a sensitive indicator of tumour biology, showed no clear difference between breast tumours from New Zealand patients and those from non-New Zealand patients. This suggests that other factors may contribute to the high and increasing breast cancer incidence in New Zealand compared to international populations.

Gene-by-environment interactions of the CLOCK, PEMT, and GHRELIN loci with average sleep duration in relation to obesity traits using a cohort of 643 New Zealand European children.

OBJECTIVES: Modern technology may have desensitised the 'biological clock' to environmental cues, disrupting the appropriate co-ordination of metabolic processes. Susceptibility to misalignment of circadian rhythms may be partly genetically influenced and effects on sleep quality and duration could predispose to poorer health outcomes. Shorter sleep duration is associated with obesity traits, which are brought on by an increased opportunity to eat and/or a shift of hormonal profile promoting hunger. We hypothesised that increased sleep duration will offset susceptible genetic effects, resulting in reduced obesity risk. METHODS: We recruited 643 (male: 338; female: 305) European children born to participants in the New Zealand centre of the International Screening for Pregnancy Endpoints sleep study. Ten genes directly involved in the circadian rhythm machinery and a further 20 genes hypothesised to be driven by cyclic oscillations were evaluated by Sequenom assay. Multivariable regression was performed to test the interaction between gene variants and average sleep length (derived from actigraphy), in relation to obesity traits (body mass index (BMI) z-scores and percentage body fat (PBF)). RESULTS: No association was found between average sleep length and BMI z-scores (p = 0.056) or PBF (p = 0.609). Uncorrected genotype associations were detected between STAT-rs8069645 (p = 0.0052) and ADIPOQ-rs266729 (p = 0.019) with differences in average sleep duration. Evidence for uncorrected gene-by-sleep interactions of the CLOCK-rs4864548 (p = 0.0039), PEMT-936108 (p = 0.016) and GHRELIN-rs696217 (p = 0.046) were found in relation to BMI z-scores but not for PBF. CONCLUSION: Our results indicate that children may have different genetic susceptibility to the effects of sleep duration on obesity. Further confirmatory studies are required in other population cohorts of different age groups.

MicroRNA profiling of ovarian granulosa cell tumours reveals novel diagnostic and prognostic markers.

BACKGROUND: The aim of this study was to explore the clinical utility of microRNAs (miRNAs) as improved markers of ovarian granulosa cell tumours (GCTs) for cancer diagnosis and prognosis prediction. Current histopathological and genetic markers, such as the presence of a FOXL2 gene mutation to distinguish between the two major subtypes are not wholly accurate and as such novel biomarkers are warranted. METHODS: The miRNA expression profiles of five formalin-fixed, paraffin-embedded (FFPE) adult-GCTs and five juvenile-GCTs were assessed using Affymetrix miRNA 3.0 Arrays and compared for differential expression. Ten miRNAs were assessed in an additional 33 FFPE tumours and four normal granulosa cell samples by quantitative RT-PCR, and their expression correlated to clinical information. RESULTS: MicroRNA array found 37 miRNAs as differentially expressed between the two GCT subtypes (p < 0.05, fold change ≥2 and among these, miRs -138-5p, -184, -204-5p, -29c-3p, -328-3p and -501-3p were validated by RT-qPCR as differentially expressed between the two GCT subtypes (p < 0.05). In addition, the expression of miR-184 was predictive of tumour recurrence in adult-GCTs, specifically for patients diagnosed with stage I and II and stage I only disease (p < 0.001 and p < 0.05, respectively). CONCLUSIONS: This study is the first to report on global miRNA expression profiles of human ovarian GCTs using FFPE tumour samples. We have validated six miRNAs as novel markers for subtype classification in GCTs with low levels of miR-138-5p correlating with early tumour stage. Low miR-184 abundance was correlated with tumour recurrence in early stage adult-GCT patients as a candidate predictive biomarker. Further studies are now needed to confirm the clinical utility of these miRNAs as diagnostic and recurrence markers, and understand their possible roles in the pathogenesis of GCTs.

Analysis of association of gene variants with obesity traits in New Zealand European children at 6 years of age.

Childhood obesity is a public health problem, which is associated with a long-term increased risk of cardiovascular disease and premature mortality. Several gene variants have previously been identified that have provided novel insights into biological factors that contribute to the development of obesity. As obesity tracks through childhood into adulthood, identification of the genetic factors for obesity in early life is important. The objective of this study was to identify putative associations between genetic variants and obesity traits in children at 6 years of age. We recruited 1208 children of mothers from the New Zealand centre of the international Screening for Pregnancy Endpoints (SCOPE) study. Eighty common genetic variants associated with obesity traits were evaluated by the Sequenom assay. Body mass index standardised scores (BMI z-scores) and percentage body fat (PBF; measured by bio-impedance assay (BIA)) were used as anthropometric measures of obesity. A positive correlation was found between BMI z-scores and PBF (p < 0.001, r = 0.756). Two subsets of gene variants were associated with BMI z-scores (HOXB5-rs9299, SH2B1-rs7498665, NPC1-rs1805081 and MSRA-rs545854) and PBF (TMEM18-rs6548238, NPY-rs17149106, ETV-rs7647305, NPY-rs16139, TIMELESS-rs4630333, FTO-rs9939609, UCP2-rs659366, MAP2K5-rs2241423 and FAIM2-rs7138803) in the genotype models. However, there was an absence of overlapping association between any of the gene variants with BMI z-scores and PBF. A further five variants were associated with BMI z-scores (TMEM18-rs6548238, FTO-rs9939609 and MC4R-rs17782313) and PBF (SH2B1-rs7498665 and FTO-rs1421085) once separated by genetic models (additive, recessive and dominant) of inheritance. This study has identified significant associations between numerous gene variants selected on the basis of prior association with obesity and obesity traits in New Zealand European children.