Analysis of the CCR5 gene coding region diversity in five South American populations reveals two new non-synonymous alleles in Amerindians and high CCR5*D32 frequency in Euro-Brazilians

The CC chemokine receptor 5 (CCR5) molecule is an important co-receptor for HIV. The effect of the CCR5*D32 allele in susceptibility to HIV infection and AIDS disease is well known. Other alleles than CCR5*D32 have not been analysed before, neither in Amerindians nor in the majority of the populations all over the world. We investigated the distribution of the CCR5 coding region alleles in South Brazil and noticed a high CCR5*D32 frequency in the Euro-Brazilian population of the Paraná State (9.3%), which is the highest thus far reported for Latin America. The D32 frequency is even higher among the Euro-Brazilian Mennonites (14.2%). This allele is uncommon in Afro-Brazilians (2.0%), rare in the Guarani Amerindians (0.4%) and absent in the Kaingang Amerindians and the Oriental-Brazilians. R223Q is common in the Oriental-Brazilians (7.7%) and R60S in the Afro-Brazilians (5.0%). A29S and L55Q present an impaired response to β-chemokines and occurred in Afro- and Euro-Brazilians with cumulative frequencies of 4.4% and 2.7%, respectively. Two new non-synonymous alleles were found in Amerindians: C323F (g.3729G > T) in Guarani (1.4%) and Y68C (g.2964A > G) in Kaingang (10.3%). The functional characteristics of these alleles should be defined and considered in epidemiological investigations about HIV-1 infection and AIDS incidence in Amerindian populations

ICAR: endoscopic skull‐base surgery

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<it>MGMT</it>, <it>GATA6</it>, <it>CD81</it>, <it>DR4</it>, and <it>CASP8</it> gene promoter methylation in glioblastoma

<p>Abstract</p> <p>Background</p> <p>Methylation of promoter region is the major mechanism affecting gene expression in tumors. Recent methylome studies of brain tumors revealed a list of new epigenetically modified genes. Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epigenetic markers and evaluate its separate and concomitant role in glioblastoma genesis and patient outcome.</p> <p>Methods</p> <p>The methylation status of <it>MGMT</it>, <it>CD81</it>, <it>GATA6</it>, <it>DR4</it>, and <it>CASP8</it> in 76 patients with primary glioblastomas was investigated. Methylation-specific PCR reaction was performed using bisulfite treated DNA. Evaluating glioblastoma patient survival time after operation, patient data and gene methylation effect on survival was estimated using survival analysis.</p> <p>Results</p> <p>The overwhelming majority (97.3%) of tumors were methylated in at least one of five genes tested. In glioblastoma specimens gene methylation was observed as follows: <it>MGMT</it> in 51.3%, <it>GATA6</it> in 68.4%, <it>CD81</it> in 46.1%, <it>DR4</it> in 41.3% and <it>CASP8</it> in 56.8% of tumors. Methylation of <it>MGMT</it> was associated with younger patient age (p < 0.05), while <it>CASP8</it> with older (p < 0.01). <it>MGMT</it> methylation was significantly more frequent event in patient group who survived longer than 36 months after operation (p < 0.05), while methylation of <it>CASP8</it> was more frequent in patients who survived shorter than 36 months (p < 0.05). Cox regression analysis showed patient age, treatment, <it>MGMT</it>, <it>GATA6</it> and <it>CASP8</it> as independent predictors for glioblastoma patient outcome (p < 0.05). <it>MGMT</it> and <it>GATA6</it> were independent predictors for patient survival in younger patients’ group, while there were no significant associations observed in older patients’ group when adjusted for therapy.</p> <p>Conclusions</p> <p>High methylation frequency of tested genes shows heterogeneity of glioblastoma epigenome and the importance of <it>MGMT</it>, <it>GATA6</it> and <it>CASP8</it> genes methylation in glioblastoma patient outcome.</p