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Developing Indigenous models of diabetes
Published in Joanna Ziarkowska, Indigenous Bodies, Cells, and Genes, 2020
The most serious harm associated with an uncritical and indiscriminate application of the thrifty gene hypothesis is downplaying the impact of historical and social factors contributing to high levels of diabetes in Indian Country. As Carolyn Smith-Morris observes, Genetic contributions to modern rates of diabetes have been overemphasized in the past, contributing to a sense that this disease is inevitable in Native American populations. It is rarer to see political-economic factors addressed, although it is possible for programs to deal with structural issues even if they cannot resolve them.(34)
Genetic Determinants of Nutrient Processing
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
The selective advantage of metabolic disease and its associated risk factors can be explained, in part, by the “thrifty gene” hypothesis [29]. Specific to the example of T2D and obesity, the “thrifty gene” hypothesis posits that there was evolutionary selection of genes related to energy storage and fat deposition that conferred benefit in times of food scarcity but which are associated with deleterious effects in a Westernized environment that is dominated by physical inactivity and excess caloric consumption. In support of this hypothesis is the finding that obesity and T2D have risen to epidemic proportions in certain ethnic groups living in a Westernized environment, compared to their native environment (e.g., Pima Indians) [30,31]. These gene-diet interactions describe the effect of dietary changes on genotype to produce a resultant phenotype or disease. This is supported by the interindividual variability observed in response to dietary modification (i.e., gene-nutrition interaction). A summary of relevant gene-nutrient interaction studies across a range of genes and dietary factors and their impact on metabolic disease is presented in Table 2.1.
Evolution of Type 2 Diabetes Mellitus
Published in David Heber, Zhaoping Li, Primary Care Nutrition, 2017
The “thrifty gene hypothesis” suggests that human evolution has selected for genes promoting efficient food collection and nutrient storage in order to promote survival during periods of famine. In the present era of food excess, these genes would be disadvantageous because they may contribute to energy storage, impaired energy expenditure, and an increased risk for the development of T2DM (Speakman 2007).
Association study of CREBRF missense variant (rs373863828:G > A; p.Arg457Gln) with levels of serum lipid profile in the Pacific populations
Published in Annals of Human Biology, 2018
Jun Ohashi, Izumi Naka, Takuro Furusawa, Ryosuke Kimura, Kazumi Natsuhara, Taro Yamauchi, Minato Nakazawa, Takafumi Ishida, Tsukasa Inaoka, Yasuhiro Matsumura, Ryutaro Ohtsuka
Of particular interest is the possibility that the rs373863828:G > A allele has been subjected to recent positive selection (Minster et al. 2016), which is consistent with the thrifty gene hypothesis proposed by Neel (1962). The thrifty gene hypothesis can explain the high prevalence of obesity in modern societies; individuals with a thrifty gene efficiently store fats and, thus, have selective advantage in times of famine (i.e. in the past), but become obese in times of an over-abundance of food (i.e. at the present time).
Genetic variants influencing obesity-related traits in Japanese population
Published in Annals of Human Biology, 2019
In 1962, James V. Neel proposed a hypothesis to explain why certain modern human populations show high susceptibility to type 2 diabetes (Neel 1962). This hypothesis, known as the ‘thrifty gene hypothesis’, proposed that the genotypes predisposed to type 2 diabetes may have been advantageous during the evolution of modern humans, in coping with starvation and fluctuating food availability. Neel’s idea was further expanded to other metabolic diseases, including obesity, and widely accepted as a working hypothesis in research related to the evolution of genes involved in metabolic diseases. Oceanians have been the subjects of these studies aimed at discovering thrifty genes, since their ancestors likely experienced starvation during dispersal in voyaging and the present Oceanians show a high prevalence of obesity (Nakayama et al. 2008; Myles et al. 2011; Naka et al. 2013). One of the probable candidates for a thrifty gene is the CREB3 regulatory factor gene (CREBRF) (Minster et al. 2016). A missense SNP of CREBRF, rs373863828, was common in obesity-prone Samoan populations, with an exceptionally large effect size on BMI; moreover, the BMI-increasing allele showed a strong signature of recent natural positive selection in Samoan genomes (Minster et al. 2016). High prevalence of this variant and its association with BMI were confirmed in other Oceanian populations (Naka et al. 2017). The obesity-prone variant of CREBRF was hypothesised to have a great advantage in surviving the voyage (Minster et al. 2016). There has not been, however, any evidence supporting that CREBRF acts as the thrifty gene in human populations other than Oceanians, since the risk allele was extremely rare in non-Oceanian populations and no other variant close to this gene had been reported to be associated with obesity-related traits. Moreover, there was no convincing evidence for a strong positive natural selection favouring thrifty genotypes of other loci. Wang and Speakman (2016) examined signatures of positive natural selection at 115 obesity-related SNPs, which were discovered by large scale GWAS, in the 1000 Genome Project populations and found that selection signatures were not observed more frequently in the obesity-related SNPs than in the randomly selected SNPs. Of the nine obesity-related SNPs with signatures of natural positive selection, five showed that alleles linked to lower BMI were selectively favourable (Wang and Speakman 2016).
The melatonin receptor 1B gene links circadian rhythms and type 2 diabetes mellitus: an evolutionary story
Published in Annals of Medicine, 2023
Hui Zhu, Zhi-jia Zhao, Hong-yi Liu, Jie Cai, Qin-kang Lu, Lin-dan Ji, Jin Xu
The thrifty gene hypothesis has sparked great interest in genetic risks for T2D among different ethnic groups over the years. Previous studies provided genetic evidence for the role of the transcription factor 7-like 2 (TCF7L2) gene in the relationship between T2DM and adaptive evolution [226,227]; the researchers observed potential positive selection for HapA (a cluster of homogeneous haplotypes in TCF7L2), which was linked with T2DM, as well as several phenotypic traits related to energy metabolism among East Asian, European and West African populations [227]. Another study in 2009 found high population differentiation for rs7901695 at TCF7L2 but failed to acquire a general signal of positive selection for 17 obesity and T2DM risk loci [228]. In addition, 58 T2DM- or obesity-associated loci from GWASs were examined in 53 different populations by geographical region; the findings implied that different populations experienced substantial variation in selection pressures on obesity and T2DM risk alleles, and no evidence was able to distinguish the ancestral or derived thirty genotypes for T2DM/obesity [229]. The specific variants tended to appear in specific populations; for example, the region containing T2DM loci exhibited predominantly group-specific differentiation between East Asians and Sub-Saharan Africans [229]. A large genetic analysis of thrifty genes in 65 T2DM index SNPs failed to identify a global signal for positive selection but detected several positively selected loci in one or more specific populations; for example, five SNPs in PROX1, GRB14, UEB2E2, IGF2BP2 and ARAP1 in African populations; three SNPs in PROX1, HMGA2 and PRC1 in European populations; and nine SNPs in NOTCH2, THADA, GRB14, WFS1, TP53INP1, TCF7L2 and PRC1 in East Asian populations [224]. Some studies have provided a potential explanation for this phenomenon: the extreme disparities in T2DM risk allele frequencies across diverse populations from Sub-Saharan Africa and from Europe to East Asia may have been caused by an adaptation to different climates, agricultural revolutions or dietary components after human mass migration [230,231]. Neel also emphasized the influences of the complex interplay of genetic and environmental factors on T2DM 36 years after proposing the thrifty gene concept; he supported the role of detrimental lifestyle changes in industrialized societies in genetic homeostasis among populations at high risk of T2DM [232].