scholarly journals A Variation in the Cerebroside Sulfotransferase Gene Is Linked to Exercise-Modified Insulin Resistance and to Type 2 Diabetes

2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
A. Roeske-Nielsen ◽  
K. Buschard ◽  
J. E. Månson ◽  
L. Rastam ◽  
U. Lindblad
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Chaperone ◽  
Population Survey ◽  
Secretory Granules ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Increased Risk

Aims. The glycosphingolipidβ-galactosylceramide-3-O-sulfate (sulfatide) is present in the secretory granules of the insulin producingβ-cells and may act as a molecular chaperone of insulin. The final step in sulfatide synthesis is performed by cerebroside sulfotransferase (CST) (EC 2.8.2.11). The aim of this study was to investigate whether two single nucleotide polymorphisms (SNP), rs2267161 located in an exon or rs42929 located in an intron, in the gene encoding CST are linked to type 2 diabetes (T2D).Methods. As a population survey, 265 male and female patients suffering from T2D and 291 gender matched controls were examined.Results. A higher proportion of T2D patients were heterozygous at SNP rs2267161 with both T (methionine) and C (valine) alleles present (49.8% versus 41.3%,P=.04). The calculated odd risk for T2D was 1.47 (1.01–2.15,P=.047). Among female controls, the homozygous CC individuals displayed lower insulin resistance measured by HOMA-IR (P=.05) than the C/T or TT persons; this was particularly prevalent in individuals who exercise (P=.03).Conclusion. Heterozygosity at SNP rs2267161 in the gene encoding the CST enzyme confers increased risk of T2D. Females with the CC allele showed lower insulin resistance.

scholarly journals In vivo reporter assays uncover changes in enhancer activity caused by type 2 diabetes associated SNPs

2020 ◽  
Author(s):  
Ada Admin ◽  
Ana Eufrásio ◽  
Chiara Perrod ◽  
Marta Duque ◽  
Fábio J.Ferreira ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Nucleotide Polymorphisms ◽  
Enhancer Activity ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Nucleotide Mutation ◽  
Reporter Assays ◽  
Coding Snp

Many single nucleotide polymorphisms (SNPs) associated to type 2 diabetes overlap with putative endocrine pancreatic enhancers, suggesting that these SNPs modulate enhancer activity and consequently, gene expression. We performed <i>in vivo</i> mosaic transgenesis assays in zebrafish to quantitatively test the enhancer activity of type 2 diabetes-associated <i>loci</i>. Six out of ten tested sequences are endocrine pancreatic enhancers. The risk variant of two sequences decreased enhancer activity, while in another two incremented it. One of the latter (rs13266634) locates in a <i>SLC30A8 </i>exon, encoding a tryptophan-to-arginine substitution that decreases <i>SLC30A8 </i>function, being the canonical explanation for type 2 diabetes risk association. However, other type 2 diabetes associated SNPs that truncate SLC30A8, confer protection to this disease, contradicting this explanation. Here, we clarify this incongruence showing that rs13266634 boosts the activity of an overlapping enhancer, suggesting a SLC30A8 gain-of-function as the cause for the increased risk for the disease. We further dissected the functionality of this enhancer finding a single nucleotide mutation sufficient to impair its activity. Overall, this work assesses <i>in vivo</i> the importance of disease-associated SNPs in the activity of endocrine pancreatic enhancers, including a poorly explored case where a coding SNP modulates the activity of an enhancer.

scholarly journals Associations between Aquaglyceroporin Gene Polymorphisms and Risk of Type 2 Diabetes Mellitus

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yijun Wang ◽  
Gang Chen ◽  
Qingyun Tu ◽  
Junxia Wu ◽  
Yu Qin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Diseases ◽  
Proteinase K ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Polymerase Chain ◽  
And Gender

Objectives. AQP7 and AQP9 represent glycerol channel in adipose tissue and liver and have been associated with metabolic diseases. We aimed to investigate the associations between genetic variants in AQP7 and AQP9 genes and the risk of type 2 diabetes (T2DM) in Chinese population. Methods. Blood samples were drawn from 400 T2DM patients and 400 age- and gender-matched controls. Genomic DNA was extracted by proteinase K digestion and phenol–chloroform extraction. Genotyping of 5 single nucleotide polymorphisms (SNPs) in AQP7 (rs2989924, rs3758269, and rs62542743) and AQP9 (rs57139208, rs16939881) was performed by the polymerase chain reaction assay with TaqMan probes. Results. The subjects with rs2989924 GA+AA genotypes had 1.47-fold increased risk of T2DM (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.06-2.04), compared to those with GG genotype, and this association remained significant after adjustment for covariates (OR 1.66, 95% CI 1.07-2.57). When compared with rs3758269 CC genotype, the subjects with CT+TT genotypes had 45% decreased T2DM risk after multivariate adjustment (OR 0.55, 95% CI 0.35-0.85). The associations were evident in elder and overweight subjects and those with central obesity. No association was observed between AQP9 SNPs and T2DM risk. Conclusions. AQP7 SNP rs2989924 and rs3758269 were associated with T2DM risk in Chinese Han population.

scholarly journals Single nucleotide polymorphisms in the gene encoding Krüppel-like factor 7 are associated with type 2 diabetes

Diabetologia ◽  
2005 ◽  
Vol 48 (7) ◽  
pp. 1315-1322 ◽  
Author(s):  
A. Kanazawa ◽  
Y. Kawamura ◽  
A. Sekine ◽  
A. Iida ◽  
T. Tsunoda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Single Nucleotide

scholarly journals In vivo reporter assays uncover changes in enhancer activity caused by type 2 diabetes associated SNPs

2020 ◽  
Author(s):  
Ada Admin ◽  
Ana Eufrásio ◽  
Chiara Perrod ◽  
Marta Duque ◽  
Fábio J.Ferreira ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Nucleotide Polymorphisms ◽  
Enhancer Activity ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Nucleotide Mutation ◽  
Reporter Assays ◽  
Coding Snp

Many single nucleotide polymorphisms (SNPs) associated to type 2 diabetes overlap with putative endocrine pancreatic enhancers, suggesting that these SNPs modulate enhancer activity and consequently, gene expression. We performed <i>in vivo</i> mosaic transgenesis assays in zebrafish to quantitatively test the enhancer activity of type 2 diabetes-associated <i>loci</i>. Six out of ten tested sequences are endocrine pancreatic enhancers. The risk variant of two sequences decreased enhancer activity, while in another two incremented it. One of the latter (rs13266634) locates in a <i>SLC30A8 </i>exon, encoding a tryptophan-to-arginine substitution that decreases <i>SLC30A8 </i>function, being the canonical explanation for type 2 diabetes risk association. However, other type 2 diabetes associated SNPs that truncate SLC30A8, confer protection to this disease, contradicting this explanation. Here, we clarify this incongruence showing that rs13266634 boosts the activity of an overlapping enhancer, suggesting a SLC30A8 gain-of-function as the cause for the increased risk for the disease. We further dissected the functionality of this enhancer finding a single nucleotide mutation sufficient to impair its activity. Overall, this work assesses <i>in vivo</i> the importance of disease-associated SNPs in the activity of endocrine pancreatic enhancers, including a poorly explored case where a coding SNP modulates the activity of an enhancer.

scholarly journals A Novel Polymorphism (rs35612982) in CDKAL1 Is a Risk Factor of Type 2 Diabetes: A Case-Control Study

2019 ◽  
Vol 44 (6) ◽  
pp. 1313-1326 ◽  
Author(s):  
Yanni Tian ◽  
Jing Xu ◽  
Ting Huang ◽  
Jiaqi Cui ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Case Control Study ◽  
Insulin Level ◽  
Northwest China ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk ◽  
The Status ◽  
Control Study

Background: The interaction of environmental factors and genetic factors may contribute to the risk of type 2 diabetes (T2D). We aimed to investigate whether age, gender, body mass index (BMI) and lifestyle factors have an effect on the association between the CDKAL1 polymorphisms and T2D. Methods: Eight single nucleotide polymorphisms in CDKAL1 were genotyped by Agena MassARRAY in 508 T2D patients and 503 controls. The association between the CDKAL1 polymorphisms and T2D was evaluated using logistic regression model by calculating OR and 95% CIs. Results: We found a significant association between CDKAL1 polymorphisms (rs4712523, OR 1.42, p = 9.44 × 10–5; rs4712524, OR 1.38, p = 3.28 × 10–4; rs10946398, OR 1.43, p = 6.21 × 10–5; rs7754840, OR 1.43, p = 6.33 × 10–5; rs35612982, OR 1.34, p = 0.0010; and rs10440833, OR 1.32, p = 0.0018) and T2D risk among the Han population from Northwest China. We also found that genetic variants of CDKAL1 could modify the risk of T2D that might be influenced by age, BMI and the status of smoking and drinking. Besides, rs35612982-CT (p = 0.038) and rs10440833-AT (p = 0.044) genotypes were higher insulin level. Conclusion: CDKAL1 rs35612982 (C/T) polymorphism, as a new polymorphism, was associated with the increased risk of T2D in the Han Chinese population. Moreover, the contribution of CDKAL1 polymorphisms to T2D risk seems to be associated with age, gender, BMI, smoking and drinking.

Abstract P163: Are Coronary Artery Disease and Type 2 Diabetes Causally Related to Age of Menopause?

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
N. Charlotte Onland-Moret ◽  
Claire Lovern ◽  
Marlies Voorhuis ◽  
Ching-Ti Liu ◽  
Frank J Broekmans ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Risk ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Natural Menopause ◽  
Single Nucleotide ◽  
Genotyping Array ◽  
Genetic Risk Scores ◽  
Increased Risk

Background: Women who enter the menopause at a younger age, are at an increased risk of cardiovascular disease (CVD) and type 2 diabetes (T2D) in later life. However, we have previously reported that development of an unfavourable cardiovascular risk profile premenopausally accelerates the onset of menopause. Furthermore, we reported that women who were diagnosed with diabetes at a very young age also reached menopause earlier. Hence, the direction of the relationship between coronary heart disease (CHD), T2D and the onset of menopause is unclear, and whether the associations are causal is also unclear. Hypothesis: In this study we hypothesize that CHD and/or T2D are causally related to the age of menopause, and studied this using genetic risk scores for CHD and T2D. Methods: Single nucleotide polymorphisms which had previously reached genome-wide significance for CHD and T2D were, individually and as a genetic risk score, tested for an association with age at natural menopause in over 50,000 women from three large consortia: the ITMAT/Broad/CARe (IBC) consortium, the ReproGen consortium, and the EPIC-InterAct consortium. From these consortia all women with a known age at natural menopause between 40 and 60 years were included. We used the genotyping array of the IBC consortium for the selection of the SNPs. The IBC array is a gene-centric genotyping array developed for replication and fine mapping and incorporates about 50K SNPs that capture information on 2000 genetic regions related to cardiovascular, inflammatory, and metabolic regions. The selected SNPs were also requested for analyses in the other two consortia. A total of 18 single nucleotide polymorphisms for CHD and 28 for T2D were selected. In the EPIC-InterAct study we used these SNPs to calculate unweighted individual level genetic risk scores. Results: No statistically significant associations were found for any of the CHD SNPs, nor for the T2D SNPs, nor for the genetic risk scores. Conclusions: Previous findings that women with an increased risk of CHD or T2D also have an increased risk of entering the menopause at younger ages, could not be supported by our data. Furthermore, the association between cardiometabolic disease and earlier timing of menopause does not seem to be causal. However, this finding does not exclude the possibility that the reverse association can be causal.

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