TNF promoter SNP variation in Amerindians and white-admixed women from Misiones, Argentina.

The aim of this study is to describe genetic variation in the TNF promoter in the ethnically diverse population of Misiones, north-eastern Argentina. We analysed 210 women including 66 Amerindians of the Mbya-Guarani ethnic group and 144 white-admixed individuals from urban and rural areas of Misiones. Their DNA samples were surveyed for TNF polymorphisms -376 A/G, -308 A/G -244 A/G and -238 A/G by PCR amplification and direct sequencing and for the Amerindian marker -857 C/T by real-time PCR. Our main findings are as follows:(i) a distinctive pattern of Single Nucleotide Polymorphism (SNP) distribution among these groups, (ii) genetic differentiation between the Mbya-Guarani and the white-admixed populations (P < 0.05), (iii) lower gene diversity (~0.05) in Mbya-Guarani compared with the white-admixed group (~0.21); and (iv) linkage disequilibrium between the -376A and -238A SNPs in white-admixed populations. These data highlight the principal role of population history in establishing present-day genetic variation at the TNF locus and provide a framework for undertaking ethnographic and disease association studies in Misiones.

Physical status of the E2 human papilloma virus 16 viral gene in cervical preneoplastic and neoplastic lesions.

BACKGROUND: Integration of human papilloma virus (HPV) 16 DNA is considered an important genetic change in cervical lesion progression towards ICC. The viral E2 gene is often disrupted by this process, releasing suppression of viral E6/E7 oncogenes, a key factor for oncogenic progression. OBJECTIVES: To evaluate the physical status of HPV 16 E2 gene in cervical preneoplastic and neoplastic lesions and its relation with lesion severity. STUDY DESIGN: A sensitive PCR approach for the detection of an intact E2 HPV 16 gene in infected epithelial cells from the cervix with low grade squamous intraepithelial lesion (LGSIL), high grade squamous intraepithelial lesion (HGSIL) and invasive cervical carcinoma (ICC) diagnosis was applied. The correlation between gene disruption and lesion stage was examined. RESULTS: Sixty-two LGSIL, 39 HGSIL and 24 ICC samples were analyzed. Fifty-seven LGSIL [92%], 13 HGSIL [33%] and 4 ICC [17%] showed results compatible with an intact E2 gene, while 5 LGSIL [8%], 26 HGSIL [67%] and 20 ICC [83%] samples gave no signal. CONCLUSIONS: HPV 16 E2 gene disruption showed a positive correlation with cervical lesion progression, particularly from LGSIL to HGSIL. Although additional genetic events are very likely to be needed for HGSIL to ICC progression, the E2 gene disruption is a putative early marker to consider in the prognostic analysis of HPV 16 chronically infected women.

[Prevalence of cervical infection by human papilloma virus (HPV) in the Caucasian and Guaraní populations residing in the province of Misiones, Argentina]. / Prevalencia de la infección cervical por virus papiloma humano (HPV) en población caucásica y guaraní, residente en la provincia de Misiones, Argentina.

A genital infection with human papillomavirus (HPV) of a high risk type is necessary for the development of cervical carcinoma. HPV viral distribution among diverse world populations is not homogeneous, viral reservoirs having been detected in particular regions that can interact when humans engage in active contacts. Such viral dynamics alters the population cervical cancer relative risk, particularly when the prevalence of HPV oncogenic risk types is high. We have compared women exposed to different social, cultural and environmental conditions regarding cervical HPV infection, analyzing two populations from Misiones, Argentina: White urban women and--Guarani indian women living in the rain forest. Demographic, clinical and sexual behavior data were collected and cytological, colposcopical and virological analysis performed. Detection and genotypification of HPV was performed by PCR-RFLP. The prevalence for generic HPV infection found was high in both populations, urban women: 43%, Guarani indians: 60%, with a statistically significant difference. These values were positively associated to age of first intercourse, number of male partners and smoking history. HPV type-specific prevalences showed a relative homogeneity between populations when the main representatives of the high risk (16 and 18: 23%) and low risk (6 y 11: 12%) types were grouped together. However, the presence of other viral types was notoriously different, representing only 9% in urban women and 29% in Guarani indians with particularly high risk HPV types (33, 35, 39, 45, 51, 52, 58, 67, 68). This situation might be of importance for future viral dynamics, phylogenetic and vaccine formulation studies.

Human papillomavirus cervical infection and associated risk factors in a region of Argentina with a high incidence of cervical carcinoma.

OBJECTIVE: To assess the prevalence and potential risk factors associated with human papillomavirus (HPV) cervical infection among women residing in a region of northeastern Argentina with a high incidence of cervical cancer. METHODS: A case-control study of 330 women participating in a cervical cytological screening program conducted in Posadas city, Misiones, Argentina, from February 1997 to November 1998 was carried out. Standardized questionnaires were administered, and clinical examination including colposcopy was performed. Fresh endocervical specimens for HPV DNA detection by generic polymerase chain reaction were collected and the products typed by dot-blot hybridization. RESULTS: Human papillomavirus DNA was found in 61% of samples analyzed (185/301). Samples with normal cytology had a 43% infection rate (85/199), while those classified as low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and invasive cervical carcinoma had an infection rate of 96% (53/55), 100% (29/29), and 100% (18/18), respectively. Human papillomavirus typing showed a 64% (118/185) prevalence of type 16 among all the infected population analyzed; type 16 was detected among 49% (42/85) of infected samples with normal cytology and in an average of 74% (74/100) with abnormal cytology. Sexual behavior, residence in southern Paraguay, and history of a previous sexually transmitted diseases were the main risk factors associated with high-grade cervical lesions. CONCLUSIONS: An elevated prevalence of HPV infection was detected in this population, which also has a high incidence of cervical cancer. The broad distribution of high-risk HPV type 16 in women with normal cytology and colposcopy suggests that viral infection is an important determinant of regional cancer incidence.

Prevalencia de la infección cervical por virus papiloma humano (HPV) en población caucásica y guaraní, residente en la provincia de Misiones, Argentina / [Prevalence of cervical infection by human papilloma virus (HPV) in the Caucasian and Guaraní populations residing in the province of Misiones, Argentina]

A genital infection with human papillomavirus (HPV) of a high risk type is necessary for the development of cervical carcinoma. HPV viral distribution among diverse world populations is not homogeneous, viral reservoirs having been detected in particular regions that can interact when humans engage in active contacts. Such viral dynamics alters the population cervical cancer relative risk, particularly when the prevalence of HPV oncogenic risk types is high. We have compared women exposed to different social, cultural and environmental conditions regarding cervical HPV infection, analyzing two populations from Misiones, Argentina: White urban women and--Guarani indian women living in the rain forest. Demographic, clinical and sexual behavior data were collected and cytological, colposcopical and virological analysis performed. Detection and genotypification of HPV was performed by PCR-RFLP. The prevalence for generic HPV infection found was high in both populations, urban women: 43

, with a statistically significant difference. These values were positively associated to age of first intercourse, number of male partners and smoking history. HPV type-specific prevalences showed a relative homogeneity between populations when the main representatives of the high risk (16 and 18: 23

) types were grouped together. However, the presence of other viral types was notoriously different, representing only 9

in urban women and 29

in Guarani indians with particularly high risk HPV types (33, 35, 39, 45, 51, 52, 58, 67, 68). This situation might be of importance for future viral dynamics, phylogenetic and vaccine formulation studies.

) and low risk (6 y 11: 12