Common genetic variation near melatonin receptor MTNR1B contributes to raised plasma glucose and increased risk of type 2 diabetes among Indian Asians and European Caucasians.
Level 3 - non-randomized controlled study
Observational genetic association study across multiple cross-sectional and case-control cohorts
PubMed 19651812 · doi:10.2337/db08-1805
What was done
Genome-wide association studies for fasting plasma glucose were performed in 5,089 nondiabetic Indian Asians (Illumina Hap610 BeadChip) and 2,385 Indian Asians including 698 with type 2 diabetes (Illumina 300 BeadChip). Results were compared with findings from 4,462 European Caucasians. Associations with fasting glucose and type 2 diabetes risk were assessed across candidate loci, including MTNR1B, GCK, GCKR, and G6PC2.
What was found
Three SNPs near MTNR1B were associated with glucose among Indian Asians at P < 5 x 10^-8. The strongest association was rs2166706 (combined P = 2.1 x 10^-9). Risk allele frequency and effect sizes for rs2166706 were similar between Indian Asians and European Caucasians: frequency 46.2% vs. 45.0% (P = 0.44); fasting glucose increase 0.05 mmol/l (95% CI 0.01-0.08) vs. 0.05 mmol/l (95% CI 0.03-0.07) per risk allele copy (P = 0.84). The rs2166706 SNP was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06-1.38] per allele copy; P = 0.006). SNPs at GCK, GCKR, and G6PC2 were also associated with glucose in Indian Asians, with higher risk allele frequencies for rs1260326 (GCKR) and rs560887 (G6PC2) compared to European Caucasians.
Why it matters
This study demonstrates that common genetic variation in MTNR1B and other key glucose loci contributes to glycemic variation and type 2 diabetes risk in Indian Asians, showing conserved genetic architecture between Indian Asian and European populations.
Limits
The abstract reports on cross-sectional genetic associations without longitudinal outcome data or functional biological validation. The type 2 diabetes analysis in Indian Asians was limited to 698 cases, and the study did not evaluate gene-environment interactions.
Cited by
- supports Approximately one-third of the human population carries the melatonin receptor MTNR1B genetic variant associated with altered glucose regulation.