Haplotypic cluster of fatty acid desaturase genes FADS1, FADS2 and type 2 diabetes mellitus in Yakutsk

BACKGROUND: According to the International Diabetes Federation (IDF) in 2021, one in ten adults worldwide suffers from diabetes, of which 90% have type 2 diabetes (T2D). Numerous studies indicate that blood PUFA levels affect lipid metabolism. Blood PUFA levels are affected not only by their dietary intake, but also by their metabolism by desaturase enzymes encoded by the fatty acid desaturase 1 (FADS1) and fatty acid desaturase 2 (FADS2) genes. AIM: To study the contribution of the FADS1, FADS2 genes to the risk of developing type 2 diabetes mellitus among the Yakut population. MATERIALS AND METHODS: A total of 541 volunteers, ethnic Yakuts up to the third generation, participated in the study. The sample of patients with type 2 diabetes mellitus consisted of 95 patients from the endocrinology department of the Republican Hospital No. 2 of the State Budgetary Institution “Emergency Medical Care Center”. The comparison group was a sample of 446 volunteers without chronic diseases. A group of healthy Yakuts was divided into subgroups based on body mass index (BMI). Single nucleotide polymorphisms were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis. RESULTS: The present study established a high frequency of ancestral alleles for SNP rs174537 (72.8 - 78.1%), for SNP rs174546 (71.3–78.1%) and for the deletion rs3834458 (72.8–77.5%) in Yakut populations. Analysis of the strength of the association of alleles and genotypes of the FADS1 / FASD2 genes with type 2 diabetes did not show statistically significant values. Analysis of pairwise linkage disequilibrium and assessment of haplotypes for the studied polymorphisms was r2=0.93-1.00. An association of the TTT haplotype with type 2 diabetes mellitus, which was 14.5 times more common in patients, was revealed. CONCLUSION: The results of this study may provide input for future nutrition and diet research to examine the effects of dietary PUFA exposure on the epigenetic regulation of PUFA biosynthesis and metabolism. Further work is needed to elucidate the specific mechanisms by which the FADS gene cluster and diet influence LC PUFA levels in humans and how they influence inflammation and disease.