Genome-wide association studies (GWAS) have examined large groups of people with diabetes susceptibility. One research group that demonstrated the inverse relationship between MLT and insulin (Boden et al., 1996) also observed an association between a disruption in circadian insulin secretion and reduced glucose uptake in first degree relatives of T2D patients (Boden et al., 1999). These researchers hypothesized that disruption to the circadian rhythm of insulin secretion may be an underlying cause for the development of T2D, and also this significant finding in close relatives of T2D patients is particularly relevant to the genetic studies.
Recently, more genetic evidence has come to light, revealing a convincing link between genetic…show more content… MTNR1B locus variants that have been associated with T2D include rs1387153, rs2166706, rs2166706, rs10830962, rs4753426 (all in the 5’ promoter region), rs3781638, rs10830963 (in intron 1), and rs8192552 (in exon 1, resulting in a non-synonymous mutation G24E), all of which result in altered fasting plasma glucose (Prokopenko et al., 2009, Staiger et al., 2008, Lyssenko et al., 2009, Bouatia-Naji et al., 2009, Ronn et al., 2009, Sparso et al., 2009, Langenberg et al., 2009, Reiling et al., 2009, Chambers et al., 2009, Kelliny et al., 2009, Takeuchi et al., 2010, Andersson et al., 2010, Kim et al., 2011, Kan et al., 2010, Huopio et al., 2013, Song et al., 2011, Dietrich et al., 2011, Vlassi et al., 2012, Holzapfel et al., 2011) and rs1387153, rs2166706, and rs10830963 were directly associated with an elevated risk of T2D (Prokopenko et al., 2009, Lyssenko et al., 2009, Bouatia-Naji et al., 2009, Ronn et al., 2009, Sparso et al., 2009, Chambers et al., 2009, Takeuchi et al., 2010, Kim et al., 2011, Kan et al., 2010, (Mao et al., 2012) in both adults and children of different ethnicities. While the mechanisms are not completely understood, these polymorphisms may affect beta cell function in a number of ways, including altering glucose-stimulated insulin secretion, proinsulin conversion, incretin sensitivity and/or secretion (Mussig et al., 2010). The odds ratio for current or future development of T2D was moderate, similar to other genes associated