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Identification of Genetic Variants of Human Papillomavirus in a Group of Mexican HIV/AIDS Patients and Their Possible Association with Cervical Cancer.

ABSTRACT: Infections caused by the human immunodeficiency virus (HIV) and human papillomavirus (HPV) cause thousands of deaths worldwide each year. So far, there has been no consensus on whether there is a direct relationship between the incidence of neoplasms and the immunosuppression caused by HIV that could help understand if coinfection increases the likelihood of cervical cancer. The objective of the study was to identify the presence of genetic variants of HPV in a group of HIV-positive women and their possible association with cervical cancer. Cervical samples were taken from HIV-positive patients for cytological analysis to identify the HPV genotype by polymerase chain reaction (PCR) and sequencing. The most prevalent L1 capsid protein mutations in the HPV genotype were analyzed in silico. Various types of HPV were identified, both high-risk (HR) and low-risk (LR). The most prevalent genotype was HPV51. Analysis of the L1 gene sequences of HPV51 isolates showed nucleotide variations. Of the samples analyzed in Puebla, Mexico, HPV51 had the highest incidence (17.5%, 7/40). Different mutations, which could be used as population markers, were detected in this area, and they have not been reported in the L1 databases for HPV51 in Mexico. Genotypes 6, 14, 86, 87, 89, and 91, not detected or reported in samples from patients with HPV in Mexico, were also identified. Data from the population analyzed suggest no direct relationship between HIV immunosuppression and cervical cancer, regardless of the high- or low-risk HPV genotype. Furthermore, it is possible to develop regional population markers for the detection of HPV based on the mutations that occur in the sequence of nucleotides analyzed.

SUBMITTER: Ortiz-Gutierrez F

PROVIDER: S-EPMC8702602 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To investigate the relationship between single nucleotide polymorphisms (SNPs) in human papillomavirus (HPV) receptor associated genes and HPV susceptibility and clinical outcomes in Chinese women, from October 2016 to March 2020, a total of 3,066 women were recruited for a 3-year prospective population-based cervical cancer screening clinical trial. The primary endpoint was histological cervical intraepithelial neoplasia 2 and worse (CIN2+). Twenty-nine SNPs of HPV receptor associated genes on women with available cytology residual samples at baseline were detected using MALDI-TOF MS. Eligible data were available for 2,938 women. Rs16894821 (GG versus AA, OR =1.71 [1.08 to 2.69]) and rs724236 (TT versus AA, OR = 1.73 [1.14 to 2.62]) in SDC2 were significantly related to the HPV susceptibility. And rs2575712 (TT versus GG, OR = 2.78 [1.22 to 6.36]) in SDC2 was associated with increased HPV 16/18 susceptibility. Four SNPs (rs1047057 and rs10510097 in FGFR2 gene, rs2575735 in SDC2 gene, and rs878949 in HSPG2 gene) were significantly associated with persistent HPV infection. Importantly, the genotypes of rs16894821 under recessive model (GG versus AA/AG, OR = 2.40 [1.12 to 5.15]) in SDC2 and rs11199993 under dominant model (GC/CC versus GG, OR = 1.64 [1.01 to 2.68]) in FGFR2 were significantly associated with the disease progression. Finally, SNPs showed comparable efficacy in detecting CIN2+ for the women infected with non-HPV16/18 compared with cervical cytology (sensitivity: 0.51 [0.36 to 0.66] versus 0.44 [0.30 to 0.60], specificity: 0.96 [0.96 to 0.97] versus 0.98 [0.97 to 0.99], positive predictive value: 0.23 [0.15 to 0.33] versus 0.33 [0.22 to 0.47], and negative predictive value: 0.99 [0.98 to 0.99] versus 0.99 [0.98 to 0.99]). SNPs in HPV receptor related genes may influence HPV susceptibilities and clinical outcomes in Chinese women. IMPORTANCE Virus receptors are known to mediate virus attachment and further lead to virus infection of the host cells. In the current study, we investigated the relationship between single nucleotide polymorphisms (SNPs) in human papillomavirus (HPV) receptor associated genes and HPV susceptibility and clinical outcomes in Chinese women, and to explore the new triaging strategy for non-16/18 high-risk HPV infection.

Project description:Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic pathologies in the world. In developing countries, such as Mexico, its prevalence represents an important public health and research issue. Determining factors triggering T2DM are environmental and genetic. While diet, exercise and proper weight control are the first measures recommended to improve the quality of life and life expectancy of patients, pharmacological treatment is usually the next step. Within every population there are variations in interindividual drug response, which may be due to genetic background. Some of the most frequent first line T2DM treatments in developing countries are sulfonylureas (SU), whose targets are ATP-sensitive potassium channels (KATP). Single nucleotide polymorphisms (SNPs) of the KATP coding genes, potassium voltage-gated channel subfamily J member 11 (KCNJ11) and ATP binding cassette subfamily C member 8 (ABCC8) have been associated with SU response variability. To date, there is little information regarding the mechanism by which these SNPs work within Mexican populations. The present study describes the distribution of three SNPs [KCNJ11 rs5219 (E23K), ABCC8 rs757110 (S1369A) and rs1799854 (-3C/T)] among Mestizo Mexican (MM) T2DM patients, and compares it with published data on various healthy subjects and T2DM populations. Through this comparison, no difference in the KCNJ11 rs5219 and ABCC8 rs757110 allelic and genotypic frequencies in MM were observed compared with the majority of the reported populations of healthy and diabetic individuals among other ethnic groups; except for African and Colombian individuals. By contrast, ABCC8 rs1799854 genomic and allelic frequencies among MM were observed to be significantly different from those reported by the 1000 Genomes Project, and from diabetic patients within other populations reported in the literature, such as the European, Asian and Latin-American individuals [T=0.704, G=0.296; CC=0.506, CT=0.397, TT=0.097; 95% confidence interval (CI); P≤0.05]; except for South Asian and Iberian populations, which may reflect the admixture origins of the present Mexican population. This genetic similarity has not been observed in the other Latin-American groups. To the best of our knowledge, this is the first study of ABCC8 rs757110 and rs1799854 SNP frequencies in any Mexican population and, specifically with diabetic Mexicans. Knowledge of the genetic structure of different populations is key to understanding the interindividual responses to drugs, such as SU and whether genotypic differences affect clinical outcome.

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Identification of Genetic Variants of Human Papillomavirus in a Group of Mexican HIV/AIDS Patients and Their Possible Association with Cervical Cancer.

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