BMAP Journal

1. Discussion

 In this study, it is hypothesized that the presence of polymorphisms in the IL6, LEPR and IL1 genes may contribute to the development of ACS, considering that these polymorphisms may exacerbate inflammatory responses and contribute to the formation of atherosclerosis. Blood donors have been selected for control groups in genetic studies as it is assumed that this group represents the general population. Authors have observed [26,27] that most randomly recruited blood donors are male, in agreement with our study. Swirta et al. (2015) [27] studying the genetic influence on coronary artery disease (CAD),  recruited Polish blood donors as control group and verified that 85.3% were male with 34.0 years old of mean age, lower than our study (47 years old). Although our results indicated no risk association between gender and / or age in developing ACS with the studied polymorphisms, this possibility should not be excluded [28,29] Chiappelli et al. (2005) [30], in a study with Italian men over 67 years old, associated IL6 C allele with AMI and suggested that this association is age-dependent. Perhaps due to the fact that adults over 65 years were not included in the present study, we were unable to observe significant differences between the frequency of IL-6 gene polymorphism and gender (p = 0.63) or age (p = 0.20). In contrast, Jin et al. (2015) [22] found no association between LEPR polymorphism and susceptibility to cardiovascular disease in Chinese men and women of 59 years old, which support our finding, despite our mean age is lower. Besides, IL1 gene polymorphism has been associated with atherosclerosis in some populations [9,29]. Iacoviello et al. (2005) [29] stated that TT genotype conferred 64% less risk of AMI development in younger women. Also, Rios et al. (2010) [9] found that CC genotype increases the risk of CAD in individuals between 50 and 56 years old.

 When comparing the genotype frequencies among Brazilian individuals from different regions, we can observe that, despite the intense miscegenation between them, the genetic characteristics in relation to the SNPs evaluated remained similar. In the North East population of this study, the genotype distributions of IL-6 gene were different (p ≤ 0.0004) when compared to other populations, although a similarity was demonstrated in relation to the population from Amazon (p = 0.69). CC genotype was less frequent (5.3%) than in Portugal (12.5%), Malaysia (7.0%) and Italy (14.3%) populations. In a study with Pakistani patients, Satti et al. (2013) [30] demonstrated that the frequency of CC genotype, IL-6 and C - reactive protein plasma levels were higher in CAD patients than in control subjects (p = 0.0025). LEPR genotype distributions from our study were different when compared to China and Egypt populations (p < 0, 0001) [12,22]. T minor allele has been associated with a significant increase in the risk of CAD [8] which was not corroborated by Jin et al. (2015) [22], since they found no association between T allele and cardiovascular disease in Chinese patients. Interestingly, there was no evidence of this allele in the study by Swellan et al. (2012) [12] in Egyptian healthy individuals. Regarding to IL1 gene, our results were similar to genotype distributions in Rio de Janeiro (p = 0.08) [16] and CT genotype was the most frequent in both population (22.4% and 9.0%, respectively). 

 The CC genotype in IL1 gene was most frequent in Portugal (44.5%), Germany (45.8%) and Italy (43.9%) populations and is associated with an higher risk for CAD because it increases levels of the corresponding inflammatory cytokine, contributing  to the progression of atherosclerotic plaque [29].The genotypic distributions evaluated in the blood donor of the present study, when compared to other populations, showed the diversity of the SNPs frequencies in other countries, evidencing the importance of genetic studies in specific population groups to establish a cause-effect relationship between genes and diseases.     

 2. Conclusions

 Knowledge regarding the frequencies of genetic polymorphisms in a particular population may be a very useful tool for understanding and assessing the risk of development of several diseases. The investigation of risk factors, as well as genetic markers for ACS, is essential for prevention, diagnosis and treatment, and can reduce morbidity and mortality. These findings may be employed for future association studies regarding these polymorphisms with the inflammatory nature of diseases. One further explanation for the differences found with other populations may be the different cultural and ethnic backgrounds, which were not analyzed. Results showed no future risk of ACS development when using IL6, LEPR and IL1 markers. However, it was not possible to identify the presence of other risk factors for ACS, apart from hypertension and diabetes, in recruited blood donors.

A study of data of Dyslipidemia, smoking, alcohol, physical inactivity and family history would be important in order to relate with genetic polymorphisms, and thus provide a better assessment of the risk of developing ACS.

 3. Acknowledgments

The authors thank the Instituto Aggeu Magalhães/Fiocruz core-facilities laboratories for the use of its technologies, the blood donors from Hemope who agreed to participate in this study and Audrey Violeta Martins de Vasconcelos for allowing access to Hemope.

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