Introduction: The SNP rs7578597 (Thr1187Ala) of THADA gene was identified in GWA studies as a novel type 2 diabetes risk locus. Nevertheless, subsequent studies of this SNP effect have been inconclusive. In some studies, rs7578597 has been associated with insulin secretion but no significant correlation with type 2 diabetes has been reported. Product of THADA gene is considered to be involved in apoptosis. Whether rs7578597 affects insulin secretion throught the apoptosis of pancreatic β-cells is, however, still unknown. We analyzed the genotype distribution of rs7578597 (TT/CT/CC) in 1084 individuals comprising 247 type 2 diabetes patiens (T2D), 275 women with gestational diabetes mellitus (GDM) and 562 non-diabetics (ND). The association of genetic variants in rs7578597 with anthropometric and biochemical parameters related to type 2 diabetes was examined.
Methods: The SNP rs7578597 was assessed by TaqMan SNP Genotyping Assay. Study cohort was anthropometrically and biochemically characterized, in subgroups GDM and ND 3 h OGTT was performed. For statistical analyses Mann-Whitney test, Chi-square test and ANOVA were used (NCSS 2004).
Results: The allelic frequencies did not differ among subgroups (minor C allele: T2D 23.5%; GDM 19.2%; ND 23.8%). C allele carriership in T2D and GDM subgroups was not associated with any of the studied parameters. Carriers of C allele in non-diabetic subgroup (ND) had decreased insulin levels: AUC insulin CC+CT vs TT P=0.047. Insulin secretion was significantly lower particularly in the late phase of OGTT: 90 min P=0.039; 120 min P=0.019.
Conclusion: We found out that the C allele carriership of rs7578597 is associated with lower insulin secretion in the Czech non-diabetic population.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported by OPPA (CZ.2.17/1.1.00/32386) and by IGA MH CR NS/10209-3/2009.
05 - 09 May 2012
European Society of Endocrinology