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Type 2 diabetes: the genetic conflict hypothesis.
S Denic1, S Emerald, M G Nicholls
1College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, PO Box 17666, United Arab Emirates. s.denic@uaeu.ac.ae
Genetic conflict between parental genes influences fetal growth and insulin resistance, explaining type 2 diabetes mellitus (DM2) risk factors like low birth weight and prevalence in certain populations.
Area of Science:
- Evolutionary biology
- Human genetics
- Epidemiology
Background:
- Low birth weight is a known risk factor for type 2 diabetes mellitus (DM2).
- Epidemiological studies show a high prevalence of low birth weight in infants of fathers with DM2.
- Modern Arab populations exhibit an exceptionally high prevalence of DM2.
Purpose of the Study:
- To propose a unifying hypothesis for DM2 risk factors based on genomic imprinting and parental conflict.
- To explain the epidemiological observations linking birth weight, paternal DM2, and population-level DM2 prevalence.
Main Methods:
- The study employs a theoretical approach, analyzing genetic conflict theory and genomic imprinting.
- It examines the role of pleiotropic genes influencing fetal growth and insulin resistance.
- Parental mating systems (polyandry vs. monandry) are considered in relation to genetic conflict intensity.
Main Results:
- Parental gene conflict, driven by differential expression of maternal and paternal genes, affects fetal growth and insulin resistance.
- Increased genetic conflict (e.g., in polyandrous systems) leads to larger birth weights.
- Reduced genetic conflict (e.g., in monandrous systems) is associated with smaller birth weights and potentially higher DM2 risk.
Conclusions:
- Parent-of-origin-biased expression of pleiotropic genes offers a potential explanation for the observed associations between birth weight, paternal DM2, and DM2 prevalence.
- Human mate selection practices, influencing genetic conflict levels, may contribute to DM2 risk and prevalence.
- This hypothesis integrates evolutionary genetics with metabolic disease epidemiology.
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