Abstract
There is a heavy burden and severity of obesity and cardiometabolic conditions that include cardiovascular disease and type 2 diabetes within Polynesian peoples of Aotearoa New Zealand. Many of these conditions have a shared manner of causation and often present as comorbid. The overall purpose of this work was to explore the genetic and environmental exposures that influence the health of Māori and Pacific peoples in Aotearoa, NZ. Thus far, a number of studies have attempted to investigate the genetic and environmental influences of obesity and cardiometabolic conditions to explore and understand possible causes for the disproportionately high prevalence in these at-risk populations with varying success.
The age of onset of these conditions manifests earlier in Pacific peoples, however studies that investigate these in younger Pasefika are especially scarce. Hence, the University of Otago in collaboration with the Pacific Trust Otago recruited a total of 260 young Pasefika participants in Aotearoa NZ whom upon informed consent provided personal information, blood samples for blood biochemistry testing and DNA for the purposes of this study. Findings herein demonstrate a high prevalence of overweight and obesity, as observed by Pacific-specific BMI standards, and a high prevalence of metabolic syndrome components in young Pasefika peoples in Aotearoa NZ. Significant associations were observed with increasing BMI, notably sex-specific associations with well-established risk factors for cardiometabolic disease. These include a negative impact on lipid biochemistry in females (increases in total cholesterol, triglycerides and low-density lipoprotein cholesterol, and a decrease in high-density lipoprotein cholesterol)
Additionally, an increase in serum urate and blood pressure in both males and females was attributed to a one unit increase in BMI. Environmental exposures associated with obesity and cardiovascular risk, whereby alcohol consumption associated with an increase in BMI and total cholesterol, and a decrease in low-density lipoprotein in females only. There was an inverse relationship between BMI and physical activity.
Obesity has a genetic basis. Polynesian-specific variants within CREBRF and LIPE were tested in young Pasefika for the first time. Findings showed that CREBRF rs373863827-A associated with an increase in BMI and anthropometric measures (waist) in females, and with taller stature in males. The effect of LIPE rs370955937 also inferred an increase of obesity risk in young Pasefika.
Finally, this study discovered a novel missense variant that promotes a favourable lipid profile in Polynesians in Aotearoa NZ. Findings established a significant association of CETP variant rs1597000001 with increased HDL-C levels, and lower LDL-C levels. In a subsample of the study cohort, heterozygous carriers of the C-allele had significantly lower CETP levels compared to non-carriers of the C-allele.
Altogether, this study presents findings on the current cardiometabolic health status of a cohort of young Pasefika living in the South Island of Aotearoa NZ, where study results suggest the future health trajectory of this demographic will be poor. Additionally, this study also identified a novel Polynesian-specific variant in CETP that lowers CETP activity with associations that suggest a favourable lipid profile, particularly increasing ‘good cholesterol’ (HDL-C); findings of which are equivalent to the effect of Mendelian CETP loss-of-function mutations.
The results presented within this thesis highlights the influence of both environmental exposures and genes, on the biology of Māori and Pacific peoples. This work highlights the importance of understanding the factors that may explain the high prevalence and impact of cardiometabolic disease in at-risk Māori and Pacific peoples. The genetic-based knowledge established herein offers an opportunity for 1) additional public health initiatives focussed on preventing and reducing obesity in at-risk populations by providing insights to the knowledge on causal drivers of increased BMI, and 2) highlights the importance of investigating population-specific genetic variants that influence cardiometabolic traits to provide insight as to genetic determinants of phenotypic differences between different ethnic communities, illuminate the molecular biology of the pathogenesis of metabolic disease
Studies such as this are very important for Māori and Pacific communities as everyone deserves biologically informed healthcare. Understanding biology through the study of genetics is of utmost importance to address genomic injustice, which is of utmost importance for equity in healthcare as we move towards an era of personalised medicine grounded in genetics. Additionally, the genetic findings from this study hopes to remove the stigma associated with cardiometabolic conditions to which Māori and Pacific peoples are susceptible.