Genetics of Type 2 Diabetes: It Matters From Which Parent We Inherit the Risk

Lyssenko, Valeriya; Groop, Leif; Prasad, Rashmi B.

doi:10.1900/rds.2015.12.233

Cited by 32 publications

(25 citation statements)

References 64 publications

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“…To date, more than 120 genetic loci have been suggested to be associated with T2DM, or with glucose and insulin levels in the European and multi-ethnic populations (Sladek et al, 2007;Zeggini et al, 2008;Dupuis et al, 2010;Imamura et al, 2011;Lyssenko et al, 2015). Of these, several loci have been shown to be associated with T2DM in different ethnic groups, whereas the remaining loci have not shown any significant effects in the ethnic populations other than those in the original reports.…”

Section: Discussionmentioning

confidence: 99%

Gas6 gene rs8191974 and Ap3s2 gene rs2028299 are associated with type 2 diabetes in the northern Chinese Han population

Kazakova

Zghuang

et al. 2017

Acta Biochim Pol

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Previous studies in other countries have shown that single nucleotide polymorphisms (SNPs) in the growth arrest-specific gene 6 (Gas6; rs8191974) and adapter-related protein complex 3 subunit sigma-2 (Ap3s2; rs2028299) were associated with an increasedrisk for type 2 diabetes mellitus (T2DM). However, the association of these loci with T2DM has not been examined in Chinese populations. We performed a replication study to investigate the association of these susceptibility loci with T2DM in the Chinese population.We genotyped 1968 Chinese participants (996 with T2DM and 972controls) for rs8191974 in Gas6 and rs2028299 near Ap3s2, and examined their association with T2DM using a logistic regression analysis. We also analyzed the correlation of genotypes and clinical phenotypes. The distribution of the T allele of SNP rs8191974 in the Gas6 gene was significantly different between T2DM cases and controls when compared with the C allele (P<0.05, OR: 0.80, 95% CI: 0.69-0.94). The occurrence of the CT genotype and the dominant model was also significantly less frequent in the T2DM cases vs. controls when compared with the CC genotype (CT vs. CC: P<0.05, OR: 0.75, 95% CI:0.62-0.90; TT+CT vs. CC: P<0.05, OR:0.75, 95% CI:0.63-0.90). In SNP rs2028299, the allele C showed no statistically significant differencein distribution between the control and T2DM groups when compared with allele A. However, in male populations, the dominant model was statistically more frequent when compared with genotype AA (CC+CA vs. AA: P<0.05, OR:1.29, 95% CI:1.02-1.64), and in obesity-stratified analysis, we also observed a significant difference in the distribution of the dominant model between the T2DM cases and controls in subjects with BMI≥24 kg/m and BMI<28kg/m (CC+CA vs. AA: P<0.05, OR: 6.33, 95% CI:4.17-9.61). In conclusion, our study shows that SNPsrs8191974 and rs2028299 are significantly associated with T2DM in the Chinese population.

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Section: Discussionmentioning

confidence: 99%

Gas6 gene rs8191974 and Ap3s2 gene rs2028299 are associated with type 2 diabetes in the northern Chinese Han population

Kazakova

Zghuang

et al. 2017

Acta Biochim Pol

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“…POE have been described in congenital heart defects [86], attention deficit-hyperactivity disorder [87], testicular germ cell tumors [88], cleft lip [89], autism [90,91], language impairment [92], type II diabetes [93,94], adiposity [95], and BMI [96]. Some of these SNPs are located in proximity to imprinted genes; further evaluation is needed to determine whether all of these effects are mediated by the~100 imprinted genes in the human genome, or whether there are additional processes that affect asymmetry in the maternal and paternal genomes.…”

Section: Non-equivalence Of Maternal Vs Paternal Allelesmentioning

confidence: 99%

Evidence for germline non-genetic inheritance of human phenotypes and diseases

Senaldi

Smith-Raska

2020

Clin Epigenet

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It is becoming increasingly apparent that certain phenotypes are inherited across generations independent of the information contained in the DNA sequence, by factors in germ cells that remain largely uncharacterized. As evidence for germline non-genetic inheritance of phenotypes and diseases continues to grow in model organisms, there are fewer reports of this phenomenon in humans, due to a variety of complications in evaluating this mechanism of inheritance in humans. This review summarizes the evidence for germline-based non-genetic inheritance in humans, as well as the significant challenges and important caveats that must be considered when evaluating this process in human populations. Most reports of this process evaluate the association of a lifetime exposure in ancestors with changes in DNA methylation or small RNA expression in germ cells, as well as the association between ancestral experiences and the inheritance of a phenotype in descendants, down to great-grandchildren in some cases. Collectively, these studies provide evidence that phenotypes can be inherited in a DNA-independent manner; the extent to which this process contributes to disease development, as well as the cellular and molecular regulation of this process, remain largely undefined.

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“…So far, many susceptibility and predisposition genetic loci have been described and found to be influenced by other environmental factors such as obesity and life style effects. 84,103,129,130 However, there are an increasing molecular evidence that emphasized on the role of some variants in coding regions as causative genes that associated with T2D. 112,131,132 The sibling-relative risk for T2D is 3 compared with 15 for T1D.…”

Section: Genetics and Architecture Of T2dmentioning

confidence: 99%

Genetic predisposition in type 2 diabetes: A promising approach toward a personalized management of diabetes

Sirdah

Reading

2020

Clinical Genetics

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Diabetes mellitus, also known simply as diabetes, has been described as a chronic and complex endocrine metabolic disorder that is a leading cause of death across the globe. It is considered a key public health problem worldwide and one of four important non-communicable diseases prioritized for intervention through world health campaigns by various international foundations. Among its four categories, Type 2 diabetes (T2D) is the commonest form of diabetes accounting for over 90% of worldwide cases. Unlike monogenic inherited disorders that are passed on in a simple pattern, T2D is a multifactorial disease with a complex etiology, where a mixture of genetic and environmental factors are strong candidates for the development of the clinical condition and pathology. The genetic factors are believed to be key predisposing determinants in individual susceptibility to T2D. Therefore, identifying the predisposing genetic variants could be a crucial step in T2D management as it may ameliorate the clinical condition and preclude complications. Through an understanding the unique genetic and environmental factors that influence the development of this chronic disease individuals can benefit from personalized approaches to treatment. We searched the literature published in three electronic databases: PubMed, Scopus and ISI Web of Science for the current status of T2D and its associated genetic risk variants and discus promising approaches toward a personalized management of this chronic, non-communicable disorder.

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Genetics of Type 2 Diabetes: It Matters From Which Parent We Inherit the Risk

Cited by 32 publications

References 64 publications

Gas6 gene rs8191974 and Ap3s2 gene rs2028299 are associated with type 2 diabetes in the northern Chinese Han population

Gas6 gene rs8191974 and Ap3s2 gene rs2028299 are associated with type 2 diabetes in the northern Chinese Han population

Evidence for germline non-genetic inheritance of human phenotypes and diseases

Genetic predisposition in type 2 diabetes: A promising approach toward a personalized management of diabetes

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