Michele Milanese

DEFB1 gene polymorphisms and increased risk of HIV-1 infection in Brazilian children

In our study we analysed three single nucleotide polymorphisms (SNPs) in the 5′ untranslated region (UTR) of the DEFB1 gene, namely −52(G/A) −44(C/G) and −20(G/A), in three groups of northeastern Brazilian children in order to assess their role in HIV-1 infection. Our results allowed us to hypothesize that the SNPs located in the 5′ UTR of the DEFB1 gene can be employed as a marker of risk for HIV-1 infection.

Transcriptional effect of DEFB1 gene 5' untranslated region polymorphisms

To the Editor: Human β-defensin-1 (hBD-1) has been shown to be a candidate tumor suppressor gene by Sun et al. ( [1][1]) who reported that single nucleotide polymorphisms (SNP) in the DEFB1 gene are able to modify the transcriptional activity of hBD-1 promoter. In particular, the − 44C/G SNP was

Prevalence of autoimmune thyroid disease and thyroid dysfunction in young Brazilian patients with type 1 diabetes.

Abstract:  Patients with an autoimmune condition are known to be at higher risk of developing other autoimmune disorders. Type 1 diabetes may be associated with additional autoimmune disorders including autoimmune thyroid disease. The aim of this study was to investigate the prevalence of thyroid autoantibodies in a group of children, adolescents, and young adults with type 1 diabetes from northeastern Brazil as well as their significance for the development of thyroid disorders. The study design was cross‐sectional and descriptive, analyzing young people with a previous type 1 diabetes diagnosis. Two hundred and fourteen children and adolescents with prior diagnosis of type 1 diabetes were evaluated. Antibodies to thyroperoxidase (anti‐TPO) were determined in all patients and thyroid‐stimulating hormone (TSH) levels. The anti‐TPO antibody test was positive in 54 out of the 214 patients studied, resulting in an overall prevalence of 25.2%. Among the anti‐TPO‐positive subjects, females were predominant (72%) over males (28%) (p < 0.001). A total of 55.5% patients with positive anti‐TPO antibodies had abnormal TSH levels. Clinically significant hypothyroidism was found in 29.6% and subclinical hypothyroidism in 22.2% of patients with positive anti‐TPO. Hyperthyroidism was present in only 3% of them. Our results demonstrate the high prevalence of autoimmune thyroiditis in patients with type 1 diabetes and the need for these patients of regular screening to make a precocious diagnosis of thyroid dysfunction.

DEFB-1 genetic polymorphism screening in HIV-1 positive pregnant women and their children

Objective. In our study we evaluated the frequency of three SNPs (−52 G/A, −44 C/G; −20 G/A) in the 5′ UTR of DEFB-1 gene, in a cohort of 130 HIV-1 infected mothers and their children, collected by the Italian group SIGO in Obstetrics and Gynecology. Methods. The three SNPs (−52 G/A, −44 C/G; −20 G/A) in the 5′ UTR of DEFB-1 gene were genotyped by direct sequencing of PCR products. Results. The C allele at position −44 was shown to be significantly different in both HIV-1 positive mothers and their children when compared to the healthy controls. The odds ratio for −44 C allele in children born to HIV-1 infected mothers is 7.09 (confidence interval 3.38–15.3) while the odds ratio for this allele in HIV-1 infected mothers is 6.42 (confidence interval 3.14–13.4). Conclusions. Our results evidence a high frequency of the −44 CC allele in HIV-1 infected mothers and their children with augmented potential risk of maternal fetal transmission. This potential vertical transmission risk has been successfully prevented by antiretroviral drug treatment and cesarian section of the HIV-1 positive mothers.

MBL2 genetic screening in patients with recurrent vaginal infections

Problem  Mannose‐binding lectin (MBL) is an important component of the innate immunity, present at the mucosal level in vagina: a common pathogen’s entry point.

Copy number variation of defensin genes and HIV infection in brazilian children

Relative resistance to HIV infection has been associated with genetic polymorphisms. Both single nucleotide polymorphisms and copy number variations (CNVs) have been documented for defensins, which are natural inhibitors of HIV infection. We tested the hypothesis that these CNVs may be related to susceptibility to HIV infection and vertical transmission by evaluating the CNVs of 13 defensin genes in Brazilian HIV-infected children. Study groups included seronegative controls, HIV-infected subjects, and subjects who did not contract HIV despite exposure at the time of birth from HIV-infected mothers. We observed that the copy number of one of these genes, DEFB104, was significantly lower in HIV-positive subjects than in HIV-exposed uninfected children, suggesting DEFB104 as a candidate HIV-protective gene.

MBL2 and MASP2 gene polymorphisms in patients with hepatocellular carcinoma

Summary.  The pathogenesis of hepatocellular carcinoma (HCC) is not fully understood, but the majority of patients with HCC are associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Mannan‐binding lectin (MBL) is a collectin that can act directly as opsonine or activate MBL‐associated serine proteases (MASPs) thus initiating the antibody‐independent pathway of the complement system. In our study, we analysed two MBL2 and MASP2 functional polymorphisms (MBL2 allele A/0 and MASP2 D120G) as well as MASP2 polymorphism (Y371D) responsible for an amino acidic change in the protein in 215 HCC patients (HBV‐infected, HCV‐infected, HBV/HCV co‐infected and patients with HCC with no viral infection) and 164 healthy controls to give new insights regarding the role of these two molecules in HCC and viral infection pathogenesis. No significant association was found between MBL2 or MASP2 alleles or genotypes, neither comparing the total patients with HCC and healthy controls nor between the different groups of HCC subjects divided for type of viral infection. Also, dividing the total HCC patients group into low MBL producer (A0 and 00 genotypes) and normal producer (AA genotype) and comparing MASP2 polymorphisms in these two groups, no significant differences were found. Our data do not seem to suggest a role for MBL2 and MASP2 polymorphisms in HCC susceptibility either for HBV–HCV infection‐dependent HCC or for HCC raised as a consequence of exposure to different risk factors.

Association between MBL2 gene functional polymorphisms and high-risk human papillomavirus infection in Brazilian women

We studied the association between high-risk human papillomavirus (HPV) infection and MBL2 functional polymorphisms in a group of 180 high-risk HPV-infected women and 180 healthy control subjects. The most frequent high-risk HPV genotypes were 16 (47.2%), 31 (11.7%), 33 (5%), and 18 (2.2%), respectively. Of the 180 HPV-infected women, 99 presented with uterine cervical cancer and 81 did not. No differences in MBL2 genotype or in allelic or haplotype frequencies were found between HPV patients who developed cervical uterine cancer and those who did not. When considering combined genotypes grouped according to MBL production (designated as high, low, and deficient producers), we detected a significant difference between healthy controls and high-risk HPV-positive patients, the latter group showing increased frequencies of deficient-producer genotypes (14.4% vs 9.4% in the healthy control group, corrected p = 0.04). In conclusion, a correlation between MBL2 polymorphisms and high-risk HPV infection was found in this study.

Evolution of the hepcidin gene in primates.

BackgroundHepcidin/LEAP-1 is an iron regulatory hormone originally identified as an antimicrobial peptide. As part of a systematic analysis of the evolution of host defense peptides in primates, we have sequenced the orthologous gene from 14 species of non-human primates.ResultsThe sequence of the mature peptide is highly conserved amongst all the analyzed species, being identical to the human one in great apes and gibbons, with a single residue conservative variation in Old-World monkeys and with few substitutions in New-World monkeys.ConclusionOur analysis indicates that hepcidins role as a regulatory hormone, which involves interaction with a conserved receptor (ferroportin), may result in conservation over most of its sequence, with the exception of the stretch between residues 15 and 18, which in New-World monkeys (as well as in other mammals) shows a significant variation, possibly indicating that this structural region is involved in other functions.

ORIGINAL ARTICLE: MBL2 Genetic Screening in Patients with Recurrent Vaginal Infections

Problem  Mannose‐binding lectin (MBL) is an important component of the innate immunity, present at the mucosal level in vagina: a common pathogen’s entry point.