Variants in MTNR1B influence fasting glucose levels.
Level 3 - non-randomized controlled study
Meta-analysis of cross-sectional genome-wide association cohorts and case-control studies (graded by design analogy)
PubMed 19060907 · doi:10.1038/ng.290
What was done
Examined the leading association signals across ten genome-wide association scans for fasting glucose concentrations in 36,610 individuals of European descent, followed by a meta-analysis of type 2 diabetes risk across 13 case-control studies comprising 18,236 cases and 64,453 controls.
What was found
Variants in MTNR1B were consistently associated with fasting glucose across all ten scans. The rs10830963 G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 mmol/l (95% CI = 0.06-0.08) in fasting glucose (P = 3.2 x 10^-50) and reduced beta-cell function by HOMA-B (P = 1.1 x 10^-15). The allele increased type 2 diabetes risk with an odds ratio of 1.09 (95% CI = 1.05-1.12, P = 3.3 x 10^-7). Fasting glucose associations were also confirmed for G6PC2 rs560887 (P = 1.1 x 10^-57) and GCK rs4607517 (P = 1.0 x 10^-25).
Why it matters
Establishes MTNR1B as a key genetic regulator of fasting glucose and beta-cell function, linking melatonin receptor biology to the pathogenesis of type 2 diabetes.
Limits
The analysis was limited entirely to individuals of European descent. The individual effect size per risk allele on glucose and diabetes risk is small, and downstream molecular mechanisms were not detailed in the abstract.
Cited by
- supports Four human genetic studies published in 2009 showed that genetic variants in the melatonin receptor gene MTNR1B are associated with elevated fasting blood glucose and increased diabetes risk.