The rs2341471-G/G genotype of activating transcription factor 6 (ATF6) is the risk factor of type 2 diabetes in subjects with obesity or overweight
Main finding · T2D risk with rs2341471-G/G genotypeResult — go to the resultOdds ratio 1.61 95% CI 1.37–1.90Authors' conclusion
The present study revealed, for the first time, a strong association between the rs2341471-G/G ATF6 genotype and an increased risk of type 2 diabetes in people with obesity or overweight, regardless of known dietary risk factors. Further research is needed to support the potential of silencing the ATF6 gene as a means for the treatment and prevention of type 2 diabetes.
Study context
- Population
- Unrelated individuals from Central Russia; 4 intronic ATF6 single nucleotide polymorphisms (SNPs) (rs931778, rs90559, rs2341471, rs7,517,862) genotyped with MassARRAY-4
- Participants
- 3,229 individuals
- Comparison
- T2D patients vs healthy controls
- T2Dn = 1,569
- Healthy controlsn = 1,660reference
- Outcome
- Association of ATF6 SNPs with T2D susceptibility
Main finding
T2D risk with rs2341471-G/G genotype
Odds ratio
1.61
95% CI 1.37–1.90
PFDR < 0.0001
As reported in the abstract
Observational data: associations, not effects.
Further findings
BMI-stratified analysis: rs2341471-G/G and haplotypes CGGA and TAGA
- Associated with T2D risk exclusively in subjects with obesity or overweight
- PFDR < 0.05
Diet in obesity/overweight vs normal weight
- Higher consumption of high-carbohydrate and high-calorie diets vs normal-weight individuals
- P < 0.0001
- Influence of rs7517862 on T2D risk observed independently of dietary habits
Functional SNP annotation
- rs2341471-G predicted to create binding sites for activating transcription factors
- 18
- rs2341471-G allele associated with increased ATF6 expression
- SNP in region with enhancer activity epigenetically regulated in pancreatic islets
Original publication
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