Diabetes in Population Isolates: Lessons from Greenland

Grarup, Niels; Moltke, Ida; Albrechtsen, Anders; Hansen, Torben

doi:10.1900/rds.2015.12.320

Cited by 11 publications

(9 citation statements)

References 52 publications

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“…They found an effect of rs34861192 on serum resistin levels specific for the investigated Japanese population as this SNP is monomorphic in the EGP-CEPH Panel of dbSNP. This is also nicely demonstrated in the paper by Grarup et al which is included in this RDS Special Edition [187].…”

Section: Discussionsupporting

confidence: 56%

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

Schleinitz¹

2016

Rev Diabet Stud

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■ AbstractAdipose tissue secretes an abundance of proteins. Some of these proteins are known as adipokines and adipose-derived hormones which have been linked with metabolic disorders, including type 2 diabetes, and even with cancer. Variance in serum adipokine concentration is often closely associated with an increase (obesity) or decrease (lipodystrophy) in fat tissue mass, and it is affected by age, gender, and localization of the adipose tissue. However, there may be genetic variants which, in consequence, influence the serum concentration of a certain adipokine, and thereby promote metabolic disturbances or, with regard to the "protective" allele, exert beneficial effects. This review focuses on the genetic determination of serum levels of the following adipokines: adiponectin, chemerin, leptin, progranulin, resistin, retinol binding protein 4, vaspin, adipsin, apelin, and omentin. The article reports on the latest findings from genome-wide association studies (GWAS) and candidate gene studies, showing variants located in/nearby the adipokine genes and other (non-receptor) genes. An extra chapter highlights adipokine-receptor variants. Epigenetic studies on adipokines are also addressed.

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Section: Discussionsupporting

confidence: 56%

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

Schleinitz¹

2016

Rev Diabet Stud

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“…Therefore, our results add to the growing literature on genetic analysis in population isolates, such as the Greenlandic Inuit population. Such studies can provide a powerful approach to identify genetic variants, identify gene–environment interactions with clinical relevance, and gain knowledge into the molecular mechanisms of common disease traits [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers

et al. 2021

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Aims/hypothesis The common muscle-specific TBC1D4 p.Arg684Ter loss-of-function variant defines a subtype of non-autoimmune diabetes in Arctic populations. Homozygous carriers are characterised by elevated postprandial glucose and insulin levels. Because 3.8% of the Greenlandic population are homozygous carriers, it is important to explore possibilities for precision medicine. We aimed to investigate whether physical activity attenuates the effect of this variant on 2 h plasma glucose levels after an oral glucose load. Methods In a Greenlandic population cohort (n = 2655), 2 h plasma glucose levels were obtained after an OGTT, physical activity was estimated as physical activity energy expenditure and TBC1D4 genotype was determined. We performed TBC1D4–physical activity interaction analysis, applying a linear mixed model to correct for genetic admixture and relatedness. Results Physical activity was inversely associated with 2 h plasma glucose levels (β[main effect of physical activity] −0.0033 [mmol/l] / [kJ kg−1 day−1], p = 6.5 × 10−5), and significantly more so among homozygous carriers of the TBC1D4 risk variant compared with heterozygous carriers and non-carriers (β[interaction] −0.015 [mmol/l] / [kJ kg−1 day−1], p = 0.0085). The estimated effect size suggests that 1 h of vigorous physical activity per day (compared with resting) reduces 2 h plasma glucose levels by an additional ~0.7 mmol/l in homozygous carriers of the risk variant. Conclusions/interpretation Physical activity improves glucose homeostasis particularly in homozygous TBC1D4 risk variant carriers via a skeletal muscle TBC1 domain family member 4-independent pathway. This provides a rationale to implement physical activity as lifestyle precision medicine in Arctic populations. Data repository The Greenlandic Cardio-Metabochip data for the Inuit Health in Transition study has been deposited at the European Genome-phenome Archive (https://www.ebi.ac.uk/ega/dacs/EGAC00001000736) under accession EGAD00010001428. Graphical abstract

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“…There have been several studies conducted in Australia to identify the prevalence of PXF [143,144]. The Visual Impairment Project study cohort consisted of three distinct populations, including 3,271 urban participants aged 40 to 98 years old, 1,473 nursing home participants aged 46 to 101 years old, and 1,473 rural participants aged 40 to 95 years old [143].…”

Section: Australiamentioning

confidence: 99%

A global genetic epidemiological review of pseudoexfoliation syndrome

Hicks

Siedlecki

Haaland

et al. 2021

Exploration of Medicine

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Pseudoexfoliation (PXF) syndrome is an important public health concern requiring individual population level analysis. Disease prevalence differs by geographic location and ethnicity, and has environmental, demographic, genetic, and molecular risk factors have been demonstrated. Epidemiological factors that have been associated with PXF include age, sex, environmental factors, and diet. Genetic and molecular components have also been identified that are associated with PXF. Underserved populations are often understudied within scientific research, including research about eye disease such as PXF, contributing to the persistence of health disparities within these populations. In each population, PXF needs may be different, and by having research that identifies individual population needs about PXF, the resources in that population can be more efficiently utilized. Otherwise, PXF intervention and care management based only on the broadest level of understanding may continue to exacerbate health disparities in populations disproportionally burdened by PXF.

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Diabetes in Population Isolates: Lessons from Greenland

Cited by 11 publications

References 52 publications

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers

A global genetic epidemiological review of pseudoexfoliation syndrome

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