Abstract
Background
It is generally accepted that early detection of type 2 diabetes mellitus (T2DM) is important to prevent the development of complications and comorbidities, as well as premature death. In addition to the environmental risk factors, genetic factors may also contribute to the development of T2DM. The aim of our study is to identify single nucleotide polymorphisms (SNPs) which have an effect on the early onset of T2DM in the Hungarian population.
Methods
This study included 891 T2DM patients (438 males and 453 females). The onset of T2DM varied between 25 and 90 years of age. Pearson correlation analysis was carried out for 16 SNPs to define how they are associated with the patient's age at onset of T2DM and genetic risk score was calculated for each patient by computation of alleles identified as risk ones. Linear regression analyses were used to estimate the effect of GRS on the early onset of T2DM independently of conventional risk factors (sex, BMI and TG/HDL-C ratio).
Results
Six SNPs (rs111875 in HHEX gene, rs560887 in G6PC2 gene, rs11071657 in the C2CD4B gene, rs5219 in KCNJ11 gene, rs10830963 in MTNR1B gene and rs11671664 in GIPR gene) were identified as risk polymorphism in the correlation analysis and GRS was calculated by defining their number/subject. The GRS showed significant association (β=-0.486, p = 0.008) with younger age at onset of T2DM. The correlation of GRS with the risk of earlier onset of T2DM was significant in the male population (β= -0.581, p = 0.024) and close to significant in female one (β= -0.471, p = 0.068).
Conclusions
Our findings indicate a considerable genetic predisposition for early onset of T2DM, which is mainly attributed to the cumulative effect of 6 SNPs presently known to be susceptible alleles. This set of SNPs and the genetic risk score calculated can be used for estimating the risk of earlier onset of T2DM on individual and population levels.
Key messages
SNPs were identified to play a role in the early onset of T2DM in the Hungarian population. The genetic risk score calculated by computation of susceptible alleles can be used for risk estimation of early onset of T2DM.
Genetic Risk Score Constructed Using 14 Susceptibility Alleles for Type 2 Diabetes Is Associated With the Early Onset of Diabetes and May Predict the Future Requirement of Insulin Injections Among Japanese Individuals