Effects of APOE, APOB and LDLR variants on serum lipids and lack of association with xanthelasma in individuals from Southeastern Brazil

Abstract

Xanthelasma might be a clinical manifestation of dyslipidemia, a recognized risk factor for coronary artery disease. We investigated the association of apolipoprotein E (APOE HhaI), apolipoprotein B (APOB XbaI and Ins/Del) and LDL receptor (LDLR AvaII and HincII) gene polymorphisms with lipid profiles in 100 Brazilians with xanthelasma and 100 controls. Allele frequencies were similar in both groups. APOE, APOB and LDLR genotypes were not correlated with differences in the serum lipid profile. In individuals with xanthelasma, the APOB D allele was associated with less chance of having increased LDL-cholesterol (O.R. = 0.16, CI95% = 0.03-0.94, p = 0.042). In the control group, the APOB X+ allele was associated with less chance of having both increased total cholesterol (O.R. = 0.16, CI95% = 0.03-0.78, p = 0.023) and increased LDL-cholesterol (O.R. = 0.10, CI95% = 0.02-0.60, p = 0.012). Moreover, there was a significantly higher frequency of control individuals (68%) with elevated serum triglyceride levels, compared to patients (48%, p = 0.008). On the other hand, triglyceride levels in controls also seemed to be influenced by all other gene polymorphisms studied, an effect that might be enhanced by environmental factors.

Characterization of LDLR rs5925 and PCSK9 rs505151 genetic variants frequencies in healthy subjects from northern Chile: Influence on plasma lipid levels

“…In the studied group, the relative frequency for mutated allele T of rs5925 (LDLR) was 0.55, which is not very different for that found in individuals from southeastern Brazil, non-Hispanic white population in North America, and normocholesterolemic individuals from Italy, Germany, and the Netherlands. 8,11,27 However, this rate was different from the allele frequency found in Chilean Amerindian hypercholesterolemic subjects (0.44) from southern Chile, healthy Caucasian Brazilian individuals, and Chinese population. 7,[9][10][11] The analysis of PCSK9 mutated allele (G) frequency was 0.03, similar to the previously described for healthy and coronary disease patients from southern Chile, American Indians, European population, European elderly individuals with vascular disease, and Chinese population.…”

LDL-R AvaII and NcoI Polymorphisms: An Indirect Risk Factor for Coronary Heart Disease Among a Mendelian Population of Delhi, India

“…A higher frequency of mutated heterozygotes and homozygotes among the controls at the AvaII site indicate that the mutation in both conditions has a selective disadvantage among the cases, in which relatively higher cholesterol and body mass were observed along with significantly higher triglyceride and low-density lipoprotein. This is in concordance with earlier reports that AvaII polymorphism significantly affects LDL levels (Salazar et al 2000;Liu et al 2003;Da Luz et al 2005;Lahoz et al 2005;Nakazone et al 2009) which in turn cause coronary heart disease (Chadha et al 1997;Pongrapeeporn et al 2000). Though AvaII polymorphism was not found to be significantly associated with coronary heart disease, its significant variability for waist-hip ratio, triglyceride, and low-density lipoprotein (which are significantly associated with the disease) makes this polymorphism an important risk factor, especially in this community.…”

Single Nucleotide Polymorphisms in Apolipoprotein B, Apolipoprotein E, and Methylenetetrahydrofolate Reductase Are Associated With Serum Lipid Levels in Northern Chilean Subjects. A Pilot Study

“…This is the first study highlighting the frequency of ApoB, ApoE, and MTHFR genetic variants and their relationship with plasma lipid levels in young healthy individuals from Antofagasta city (Northern Chile). In the studied group, the relative frequency for mutated allele (T) of rs693 (ApoB) was 0.42, similar to that previously described in Chile ( Eyheramendy et al, 2015 ) and not very different of that found in individuals from Brazil ( Nakazone et al, 2009 ; Tamburus et al, 2018 ). However, this rate was different from the allele frequency found in Asian individuals as shown in Table 4 and depicted by Niu et al (2017) .…”

“…Regarding lipid profiles, no association of any of the genetic variants with total cholesterol, triglycerides, HDL-C, and LDL-C profile was found among the complete studied group of individuals, similar to those previously described (Nakazone et al, 2009;Roco et al, 2015;Mahesh et al, 2019); however, some associations appeared when the analyses were performed for each gender separately. For Apo B genetic variant, C/C genotype was associated with higher total cholesterol along with HDL-C levels in females and therefore may be a risk factor that predisposes to CVD.…”

“…For Apo B genetic variant, C/C genotype was associated with higher total cholesterol along with HDL-C levels in females and therefore may be a risk factor that predisposes to CVD. A similar association was described by Nakazone et al (2009) in a group of control individuals that consisted of 64% females; however, other authors depicted a similar association in males but not in females (Niu et al, 2017). To this respect, association of ApoB rs693 and lipid levels is controversial since this genetic variant is a silent mutation that cannot directly affect lipid metabolism; however, association with higher levels of total cholesterol, triglyceride, and LDL-C and lower levels of HDL-C has been reported, suggesting that gender, ethnicity, and health status might modulate its association to lipid levels (Peacock et al, 1992;Benn et al, 2008;Niu et al, 2017;Tamburus et al, 2018), but some of those studies presented association of high lipid levels with males, which are opposite to our findings.…”