Table 5.
Associations between type 2 diabetes CpG-SNPs that exhibit differential DNA methylation and measures of islet function including glucose-stimulated insulin secretion (SI), glucagon secretion and insulin content in human pancreatic islets
| Phenotype | SNP ID | Candidate gene | Genotype | n | Mean ± SD | β (SEM) | p value |
|---|---|---|---|---|---|---|---|
| Insulin secretion (SI) | rs11708067 | ADCY5 | AA | 48 | 7.1 ± 7.8 | 0.18 (0.08) | 0.031 |
| AG | 28 | 13.2 ± 20.1 | |||||
| GG | 2 | 16.2 ± 17.7 | |||||
| rs5015480 | HHEX | GG | 21 | 5.4 ± 5.9 | 0.14 (0.08) | 0.036 | |
| AG | 44 | 9.5 ± 10.1 | |||||
| AA | 13 | 16.1 ± 27.1 | |||||
| Glucagon (pg islet−1 h−1, 8.3 mmol/l glucose)a | rs11708067 | ADCY5 | AA | 3 | 7.0 ± 2.6 | −0.64 (0.15) | 0.027 |
| AG | 5 | 3.2 ± 2.7 | |||||
| Glucagon (pg islet−1 h−1, 16.7 mmol/l glucose) | rs2237895 | KCNQ1 | AA | 17 | 8.6 ± 10.6 | 0.26 (0.12) | 0.042 |
| AC | 19 | 23.6 ± 26.1 | |||||
| CC | 8 | 35.2 ± 42.2 | |||||
| Insulin content (ng/ng DNA) | rs564398 | CDKN2A | AA | 24 | 4.5 ± 2.5 | 0.10 (0.04) | 0.023 |
| AG | 36 | 6.9 ± 3.9 | |||||
| GG | 11 | 6.5 ± 4.1 |
Data are expressed as mean ± SD. β (SEM) and p values are from linear regression adjusted for age, sex and BMI as covariates
aData available from a subset of the cohort