THE LRP1 GENE POLYMORPHISM IS ASSOCIATED WITH INCREASED RISK OF METABOLIC SYNDROME PREVALENCE IN THE SERBIAN POPULATION
Vučinić N1,*, Stokić E1,2, Djan I3,4, Obreht D5, Veličković N5, Stankov K6, Djan M5
*Corresponding Author: Nataša Vučinić, Ph.D., University of Novi Sad, Faculty of Medicine, Department of Pharmacy, Hajduk Veljkova 3, 21000 Novi Sad, Serbia. Tel: +38121422760. Mobile: +381652452456. Fax: +38121450620. E-mail: natasa.vucinic@mf.uns.ac.rs
page: 51

DISCUSSION

Based on the results presented in our study, the LRP1 gene polymorphism was associated with the features of MetS. To the best of our knowledge, the polymorphism of exon 3 of the LRP1 gene has not yet been analyzed in the Serbian population therefore, our results represent the first step in this domain in the Serbian population. In Europe, the 14.0% frequency of the T allele, and the C allele frequency of 86.0% was found [29]. “he results of our study showed similar frequencies, where the C allele represented 80.65% and the T allele 19.35% in the total sample. Panza et al. [30] found that the frequency of allele C shows a significant decreasing trend from north to south Europe, with the associated increase in the frequency of the T allele, but only in patients with Alzheimerís disease. In the MetS group, significantly higher values of BW, BMI, WC, systolic and diastolic BP, TG, HDL cholesterol, LDL cholesterol, index of atherosclerosis, insulin level (IRI), homeostasis model assessment of insulin resistance (HOMA IR) and CRP were noticed, which was expected, especially for the WC, systolic and diastolic BP, TG and HDL cholesterol, which are the determinants of MetS by the IDF definition. Although there were no significant differences for some expected parameters such as the level of non-HDL cholesterol (p = 0.06) and fasting glucose (p = 0.06), which is one of the parameters of the IDF MetS definition, p values are very close to the threshold of significance, indicating that a (possibly) greater number of subjects could lead to significant differences in these parameters. In the MetS group, the presence of the T allele (25.4%) was found to be more frequent compared to the control group (p <0.01). Benes et al. [31] also showed a significantly higher presence of the T allele (21.0%) in the group of women suffering from breast cancer compared to the control group (p <0.05). The results revealed statistically significant connection between the presence of the CT genotype and the MetS group affiliation (p = 0.01). The TT genotype was detected only in the MetS group. The χ2 test of independence revealed a statistically significant connection between the T allele itself and MetS (p = 0.0001), indicating that the T allele may be considered as a risk factor for the development of MetS. In the MetS group, eight subjects, T allele carriers, were younger than 30 years, thus pointing out the association between the T allele and MetS emergence, also encouraging early diagnosis in order to improve quality of life and reduce the number of possible patients. Masson et al. [15] found that LRP1 plays a very important role in lipid metabolism, and its synthesis is very high during the adipocyte differentiation in mice and humans. Up to now, studies regarding the LRP1 expression and human fat tissue have been extremely scarce. There has not been any information in the literature available to us, regarding the polymorphism of exon 3 of the LRP1 gene and individual anthropometric and biochemical parameters examined in our study, therefore, our results represent the first step in revealing these relationships. The LRP1 exon 3 T allele showed a significant association with the emergence of MetS. We analyzed the connection of the five individual components of MetS with LRP1 genotypes and found that carriers of the T allele are significantly more present among subjects with elevated BMI, WC, systolic BP, TC, LDL cholesterol and index of atherosclerosis (LDL/HDL), revealed by one-way analysis of variance (ANOVA). The difference in the parameter values between the CC/CT and CC/TT genotypes and between CT/TT genotypes indicates that the presence of the T allele in the genotype is responsible for statistically significant differences. Carriers of the T allele have significantly disrupted reference values of the abovementioned parameters, and that indicates its important role in the metabolism of lipids. Further processing of the data based on the OR results indicates that presence of the T allele in patients multiplies the chance of occurrence of reference value deviations of BMI, TC and LDL cholesterol compared to C allele carriers. After adjusting for all MetS components, T allele carriers showed a significant association with the emergence of MetS by OR analysis. Our present study showed that T allele carriers of the LRP1 gene are 4.76-fold more likely to develop MetS compared to C allele carriers. In our previous study, we investigated the connection between individual alleles of the apolipoprotein E (apoE) gene on one side and the appearance of MetS on the other, as well as the correlation between the apoE gene polymorphism and each of individual anthropometric and biochemical parameters in both control and MetS test groups [32]. The frequency of the apoe4 allele was significantly higher in the MetS group. In addition, positive correlation was revealed between the presence of the apoe4 allele and all measured parameters. It was observed that the apoe4 allele was associated with a significantly increased OR of MetS disorders defined by the IDF definition. These results suggested that apoe4 allele may act as one of the determinants for development of MetS. Determining the contribution of the apoE gene polymorphism and its re ceptors, including LRP1, is very important in the study of lipid and lipoprotein metabolism [32]. Conclusions. A molecular genetic approach is the most reliable in the diagnosis of most diseases. Studies show that the implementation of routine screening, particularly in patients with hereditary load, contributes to the early diagnosis and prevention, which delays the process leading to the formation and development of CVD, diabetes, obesity, IR, thus leading to MetS, improves the quality of life and reduces the number of patients. Very early confirmation of a genetic predisposition for CVD, diabetes, obesity, IR, leading to MetS, allowed us to change habits that contribute to the emergence and development of the disease, also saving the cost of treatment [4]. The results of correlation found for the T allele of the LRP1 the gene with the determinants of MetS is not negligible, and the T allele may be considered as a risk factor for the development of MetS. Declaration of Interest. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.



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