A common variant in MTNR1B, encoding melatonin receptor 1B, is associated with type 2 diabetes and fasting plasma glucose in Han Chinese individuals

Abstract

Aims/hypothesis Recently, three groups independently reported that variation in MTNR1B, the gene encoding melatonin receptor 1B, was associated with an increased risk of type 2 diabetes, increased fasting plasma glucose and impaired insulin secretion in populations of European ancestry. In the present study, we investigated whether a single MTNR1B polymorphism was associated with type 2 diabetes in Han Chinese individuals, to elucidate whether this is a cross-populational effect. Methods The MTNR1B variant rs10830963 was genotyped in 1,165 type 2 diabetic patients and 1,105 normoglycaemic control individuals of southern Han Chinese ancestry who were residents of the metropolitan area of Shanghai. The risk of developing type 2 diabetes was calculated using a logistic regression model adjusted for age, sex and BMI. A possible association with fasting plasma glucose was analysed in the normoglycaemic control individuals using a multiple linear regression analysis with adjustments for age, sex and BMI. Results The genetic variant rs10830963 was associated with an increased risk of type 2 diabetes in our Han Chinese cohort (OR 1.16, 95% CI 1.03-1.31, p=0.015). As previously described, the risk variant was also associated with increased fasting plasma glucose, showing an increase of 0.068 mmol/l (95% CI 0.036-0.100, p=4×10 −5 ) per risk allele. Conclusions/interpretation A common variant in the MTNR1B gene is associated with an increased risk of type 2 diabetes and increased fasting plasma glucose in Han Chinese, suggesting an important role for this polymorphism in populations of different ethnic and environmental backgrounds.

Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene

“…All recently published articles on the variation in MTNR1B report an association with elevated fasting plasma glucose [56,[64][65][66]. This appears to be accounted for by impaired beta cell function; we demonstrated that this is reduced in the early phase of insulin secretion [56], while another report indicated impaired beta cell function as assessed by HOMA (HOMA-B) [65].…”

“…Thus, it is likely that the SNPs reported to be associated with MTNR1B tag the same signal. Very recently, associations of rs10830963 with elevated fasting plasma glucose and future risk of type 2 diabetes was confirmed in a Chinese population [66].…”

Common variants at the GCK, GCKR, G6PC2–ABCB11 and MTNR1B loci are associated with fasting glucose in two Asian populations

“…While some studies have shown reproducible associations [9,11,12,19,20], it remains to be further defined to what degree loci discovered in Europeans will show an association in populations of different ancestries. In addition, to localise the variant(s) responsible for an association signal, we need to generate a comprehensive list of potential causal variants in the regions of interest, i.e.…”

“…It has been reported that genetic effects explain 54.8% of the variance of glucose levels in a European population [4]. Recent progress in complex-trait genetics has allowed the identification of loci regulating FPG levels [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

The role of melatonin in diabetes: therapeutic implications

“…Moreover, diabetes is coupled with lower melatonin levels as reduction in serum melatonin and higher insulin level is observed in type 2 diabetic Goto Kakizaki rats (6). Genome-wide association studies has shown that specific single-nucleotide polymorphisms of the melatonin receptor 2 (MTNR1B) locus is linked with an increased blood glucose concentration and type 2 diabetes (8)(9)(10)(11)(12)(13). Melatonin can be able to bring anti-hyperglycemic effect either by improving insulin sensitization or by improvement of insulin secretion, or both.…”