The Hardy Weinberg equilibrium was verified
The Hardy-Weinberg equilibrium was verified in all groups using the chi-square test. Using WINPEPI 11.65, the number of carriers and non-carriers of the Δ32 allele was compared between the groups through the Pearson's chi-square test with Yates's correction. Two-tailed Fisher's test was used when appropriate. p-Value < 0.05 was set as statistically significant.
Results Table 1 shows sociodemographic data and the number of individuals included in each group. Table 2 shows HCV+ individuals data after stratification. The number/frequency of Δ32 allele carriers and non-carriers and the Imeglimin hydrochloride receptor frequencies observed in each group are shown in Table 3. Considering all individuals included in this study (controls and infected individuals), 88.76% of them showed a wild-type homozygous genotype (wt/wt), 10.72% a heterozygous genotype (wt/Δ32), and 0.52% had a variant homozygous genotype (Δ32/Δ32). A very similar distribution of genotypes was found among all groups. According to our results, and considering the absence of significantly differences regarding the frequency of the variant homozygous genotype (Δ32/Δ32) between the HCV+ and the control groups (p > 0.999), this genotype is not related to susceptibility or protection against HCV infection. Importantly, all groups were in Hardy-Weinberg equilibrium (p > 0.05 in all groups). Considering controls and infected individuals, we observed an overall Δ32 allele frequency of 5.88%. In relation to Δ32 allele carriers and non-carriers, the comparisons performed between the groups did not indicate an influence of CCR5Δ32 on the susceptibility to HCV infection, HCV/HIV co-infection, or HCV-related diseases (p-values > 0.05 resulted from all comparisons performed). These results remained unchanged when the individuals were stratified by ethnicity (data not shown). Of note, 184 individuals (~27%, Table 2) from the HCV+ group (n = 674) were infected by HCV through blood transfusions. Not even this important risk factor seems to have influenced our results.
Discussion In a study performed in Germany, Woitas et al. (2002) reported a high number of CCR5Δ32 homozygous individuals in a group of HCV+ patients in comparison to controls, which was interpreted as indicating this variant as a susceptibility factor to HCV infection. In this same study, HCV/HIV co-infected individuals also showed a higher frequency of the Δ32 allele compared to HIV mono-infected patients (Woitas et al., 2002). Although it is true that this work drew attention to the potential roles of CCR5 and CCR5Δ32 on the susceptibility to HCV infection and HCV-related diseases, due to potential confounding situations (i.e. high number of hemophiliac patients included, among others), it has generated a great debate (Klein, 2003; Mangia et al., 2003; Poljak et al., 2003; Zhang et al., 2003). In line with the criticisms made regarding this study conclusions, our results do not support an influence of the CCR5Δ32 allele on the susceptibility to HCV infection or HCV/HIV co-infection in the Brazilian population. Our findings are in agreement with several other studies evaluating different populations (Glas et al., 2003; Goyal et al., 2006; Promrat et al., 2003; Thoelen et al., 2005; Wald et al., 2004; Wasmuth et al., 2004). Moreover, previous studies of our group indicate that the ethnic background impacts the susceptibility to infectious and autoimmune diseases in the Brazilian population (Glesse et al., 2017; Schauren et al., 2013; Valverde-Villegas et al., 2017). However, in the present study, ethnic origin (based on skin-color and self-declaration) did not influence the results. The lack of a direct influence of CCR5Δ32 on the susceptibility to HCV infection is quite plausible since HCV does not use CCR5 as a cellular co-receptor to infect cells (Lindenbach and Rice, 2013; Woitas et al., 2002). Possible modifications in the susceptibility to HCV infection related to CCR5Δ32 would be associated with disturbance of the immune response induced by the low expression of the CCR5, instead of direct interactions of HCV and the CCR5 molecule.