Impact of Genetic Factors on the Age of Onset for Type 2 Diabetes Mellitus in Addition to the Conventional Risk Factors

Abstract

It is generally accepted that the early detection of type 2 diabetes mellitus (T2DM) is important to prevent the development of complications and comorbidities, as well as premature death. The onset of type 2 diabetes mellitus results from a complex interplay between genetic, environmental, and lifestyle risk factors. Our study aims to evaluate the joint effect of T2DM associated single nucleotide polymorphisms (SNPs) on the age of onset for T2DM in combination with conventional risk factors (such as sex, body mass index (BMI), and TG/HDL-C ratio) in the Hungarian population. This study includes 881 T2DM patients (Case population) and 1415 samples from the Hungarian general population (HG). Twenty-three SNPs were tested on how they are associated with the age of onset for T2DM in the Case population and 12 of them with a certified effect on the age of T2DM onset were chosen for an optimized genetic risk score (GRS) analysis. Testing the validity of the GRS model developed was carried out on the HG population. The GRS showed a significant association with the age of onset for T2DM (β = −0.454, p = 0.001) in the Case population, as well as among T2DM patients in the HG one (β = −0.999, p = 0.003) in the replication study. The higher the GRS, the earlier was the T2DM onset. Individuals with more than eight risk alleles will presumably be diabetic six and a half years earlier than those with less than four risk alleles. Our results suggest that there is a considerable genetic predisposition for the early onset of T2DM; therefore, in addition to conventional risk factors, GRS can be used as a tool for estimating the risk of the earlier onset of T2DM and stratifying populations at risk in order to define preventive interventions.

Sex-specific genetic loci linked to early and late onset type 2 diabetes

“…However, as previously reported (15), this study found that parental history and genes have a greater influence on T2D when it occurs before the age of 46 and that the influence of these factors decreases substantially when the disease is diagnosed later in life (≥46 years). Furthermore, this study also found an important difference in the association of genes, but not of parental history, with T2D between males and females (15). Here, the R 2 value was much higher in males than females (11.2% versus 4.1%), and given that the differences in gene association between males and females have not been previously reported or have only been reported for individual genes (16, 17), the differences are likely specific to the ancestry of populations in Mexico, which include a mixture of different Amerindian and European ancestries.…”

Comparative risk assessment for the development of cardiovascular diseases in the Hungarian general and Roma population

“…The high representation of CVD risk factors can be explained by the impact of environmental factors above mentioned and also by genetic causes (such as in the case of type 2 diabetes mellitus 29 ). Based on our previous studies, we can state that the higher risk/prevalence of the venous thrombosis 30 and reduced high-density lipoprotein cholesterol levels [31][32][33] are determined by genetic factors, whereas the high risk/prevalence of type 2 diabetes 34 and obesity 35 are influenced by environmental factors in the Hungarian Roma population.…”

Silencing LncRNA PVT1 Reverses High Glucose-Induced Regulation of the High Expression of PVT1 in HRMECs by Targeting miR-128-3p

“…It can be divided into type 1 diabetes in which the human body cannot synthesize and secrete insulin; type 2 diabetes in which insulin resistance is the mainstay; and other types such as gestational diabetes [2][3][4]. Different types of diabetes have different causes, such as family inheritance, environmental influence, obesity, and excessive sugar intake [5,6]. Diabetic retinopathy (DR) is the most common microvascular complication of diabetes [7,8].…”