Endocrine Abstracts

Introduction and background

According to world diabetes-focused organizations (EASD and IDF) the number of patients with type 2 diabetes mellitus (T2DM) and obesity is increasing tremendously all over the world. The FTO gene (Fat mass and obesity-associated gene) was noticed during GWAS-study at 2007, when it’s multiple polymorphic variants were detected, many of which were associated with obesity and T2DM. Significant differences in allele prevalence in between populations were observed. So minor allele rs9939609 polymorphic variant is found in 34–44% of European, 11–20% of Asian and 17% of Latin-American population. There are no similar data on Belarusian population.

Aims

The aim of the study was the detection of the most relevant genetic marker for the prediction T2DM.

Methods

We have formed 2 groups of patients to determine FTO allele frequency and it’s association with T2DM. 1st group – 116 patients with T2DM (72 female, 44 male), with an age of 51.2±8.2 years, and BMI 32.6±7.4 kg/m². 2nd – Control-group (151 female, 96 male) with an age of 34.9±9.5 years, BMI 24.1±3.9 kg/m². Peripheral blood lymphocytes were used for DNA extraction using Nucleosorb-A (“Primetech”, Belarus) kits. Genotyping of 13 FTO-gene polymorphic variants (rs10852521, rs11075990, rs1121980, rs1421085, rs1477196, rs17817449, rs3751812, rs4783819, rs7206790, rs8047395, rs9939609, rs9940128, rs9941349)was made using TaqMan® probes (Applied Biosystems, USA).

Results

The minor allele rs9939609 prevalence was 41.3% in or study, that corresponds with European population data. The strongest association with the T2DM was detected for rs9941349 (P = 0.007) plymorphysm. For minor T/T variant carriers odds ratio (OR) was 2.74, and for heterozygos – OR = 1.96. Also highly associated with T2DM were G/G rs11075990 (OR = 2.36), A/A rs1121980 (OR = 2.35), T/T rs3751812 (OR = 2.26), A/A rs9939609 (OR = 2.49), C/C rs1421085 (OR = 2.09) and A/A rs9940128 (OR = 2.19). There were no other significant associations.

Discussion

The analysis of linkage disequilibrium block showed high linkage of rs11075990, rs1121980, rs1421085, rs17817449, rs3751812, rs9939609, rs9940128, rs9941349 polymorphisms (P <0.001, r2 0.92–0.97). These variants form 2 highly prevalent haplotypes – A/G/T/T/G/T/G/C (51.4%) и G/A/C/G/T/A/A/T (42.9%), other variants do not exceed 2%, what allows genetic testing only by rs9941349 polymorphism.

Conclusion

Stable haplotype prevalence allows effective prediction of the FTO-gene polymorphism through detection of rs9941349 variant, what is highly predictive for T2DM estimation.