ABSTRACT
OBJECTIVE: The aim of this pilot study was to determine whether the low anti-müllerian hormone (AMH) serum level, due to severe endometriosis, was associated with diminished oocyte yield, poor oocyte/embryo quality and reduced in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) clinical outcomes in young patients (<37 years old). PATIENTS AND METHODS: A total of 50 IVF cycles of patients younger than 37 with severe endometriosis were retrospectively analyzed in a single center between November 2016 and July 2018. The clinical outcome was then compared to a control group of 84 patients with no story of endometriosis and normal AMH value. AMH value was evaluated within three months before the stimulation. In these two groups, number and maturation of retrieved oocytes, embryo quality, and pregnancy outcomes were evaluated and compared using Student's t-test and Fisher's test. RESULTS: The number of oocytes retrieved per cycle and the percentage of mature oocytes (MII) were significantly lower (p < 0.001) in IVF patients with severe endometriosis and AMH value ≤ 1.1 ng/ml (Group A; 3.8±2.6 retrieved oocytes, 70% MII) compared to patients without endometriosis and AMH levels > 1.1 ng/ml (Group B; 6.9±4.6 retrieved oocytes, 83% MII). On the other hand, embryo morphology, implantation rate (31% vs. 33%; p = 0.833) and pregnancy rate (50% vs. 49%; p = 1) were comparable in the two groups. CONCLUSIONS: This study shows that younger patients with an impairment of the ovarian reserve due to severe endometriosis, displayed a diminished oocyte yield but not a reduction in embryo quality and pregnancy outcomes. These results suggest that serum AMH levels should not be adopted as a criterion for discouraging these patients from undergoing IVF/ICSI treatments.
Subject(s)
Endometriosis/pathology , Fertilization in Vitro , Oocytes/pathology , Adult , Anti-Mullerian Hormone/metabolism , Female , Humans , Oocytes/metabolism , Pregnancy , Severity of Illness IndexABSTRACT
The objectives of the present study were to assess the occurrence of human adenoviruses (HAdVs) in paediatric patients with gastroenteritis in Albania and to characterize HAdV strains. Faecal specimens from children admitted with acute gastroenteritis to the Paediatric Hospital in Tirana were screened for HAdV, using broad-range primers targeting the hexon gene, in combination with species-specific primers targeting the fiber gene. Phylogenetic analysis was then performed to assess the genetic relationships among the different sequences and between the sequences of the samples and those of the prototype strains. Adenovirus DNA was detected in 33/142 samples (23.2%); 14 belonged to species F (13 HAdV-41 and 1 HAdV-40), 13 to species C (1 HAdV-1, 8 HAdV-2, and 4 HAdV-5), 5 to species B (HAdV-3), and 1 to species A (HAdV-12). Rotavirus coinfection was present in 9/33 (27.2%) positive samples. In the remaining 24 positive samples (12 enteric--F species; 12 nonenteric--A, B, or C species), HAdVs were detected as unique viral pathogens, suggesting that HAdV may be an important cause of diarrhoea in children requiring hospitalization. This is the first study investigating the presence of human adenoviruses (species A-G) as etiologic agents of viral gastroenteritis in children in Albania.
Subject(s)
Adenoviridae/genetics , Gastroenteritis/genetics , Gastroenteritis/virology , Phylogeny , Adenoviridae/classification , Adenoviridae/pathogenicity , Albania , Child , Child, Preschool , Face/virology , Female , Gastroenteritis/pathology , Genetic Variation , Humans , Infant , Male , Species SpecificityABSTRACT
Purpose: Regulation of the apoptotic process has an important role in spermatogenesis. p53 has a prominent function in apoptosis and recent data suggest a relationship between varicocele and p53 codon 72 polymorphism and male infertility. This prompted us to study the relationship between this polymorphism and spermatic parameters. Methods: We studied 134 subjects with varicocele admitted consecutively to the outpatients Department of Infertility at the University of Rome La Sapienza. We investigated in these subjects the effect of a strong apoptosis inducer, the p53 codon 72 *Arg/*Arg genotype, on spermatic parameters.The p53 codon 72 genotype was determined by DNA analysis. Results: The proportion of spermatozoa with abnormal (curvilinear) motility is higher in men with the *Arg/*Arg genotype than in men carrying the *Pro allele (p = 0.003). No statistical significant relationship has been observed with spermatozoa concentration and atypical spermatozoa. Conclusions: We conclude: the p53 codon 72*Arg/*Arg genotype, with its strong apoptotic effects, negatively influences spermatozoa motility and male fertility.
ABSTRACT
AIMS: T1D has been found associated with PTPN22 and with ACP1-ADA1 joint genotype. In the present note we have collected further data to evaluate the relative importance of the two systems and to search for possible interaction of PTPN22 with ACP1-ADA1 joint genotype. METHODS: We have studied 314 children with T1D and 770 controls from the White population of Central Italy. ACP1, ADA1 and PTPN22 genotypes were determined by DNA analysis. Chi square test of independence was performed by SPSS program and three way contingency analysis by a log-linear model. RESULTS: Both carriers of *T allele of PTPN22 and subjects with ACP1 *A/*A and *A/*B genotypes carrying ADA1 *2 allele show an increase of susceptibility to T1D. There is evidence of additive effect (p=0.0002) but not of epistatic interaction. The association of T1D with ACP1-ADA1 joint genotype is stronger (OR=2.494, 95% C.I. 1.509-4.122) as compared to that with PTPN22 (OR=1.825, 95% C.I. 1.951-2.859). CONCLUSIONS: It has been suggested that the *T variant of PTPN22 inhibits T cell receptor signaling leading to failure to delete autoreactive T cells during intrathymic selection resulting in increased susceptibility to autoimmune disorders. The joint genotype ACP1 *A/*A and *A/*B carrying the ADA1 *2 allele shows a decreased activity of ACP1 resulting in a lowering of Zap70 activity that may decrease T cell receptor signaling with an additive effects to the inhibition due to the *T variant of PTPN22.
Subject(s)
Adenosine Deaminase/genetics , Diabetes Mellitus, Type 1/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Protein Tyrosine Phosphatases/genetics , Proto-Oncogene Proteins/genetics , Alleles , Case-Control Studies , Child , Diabetes Mellitus, Type 1/immunology , Genotype , Humans , Italy , Polymerase Chain Reaction , Signal TransductionABSTRACT
Platelet-derived growth factor (PDGF) and its receptors (PDGFRs) play a key role in the regulation of the embryonic and postnatal development of male gonads. PDGF deficiency is associated with severe spermatogenic impairment. ACP1 is a phosphoprotein tyrosine phosphatase that is able to dephosphorylate PDGFR, decreasing its activity as growth factor. The enzyme is polymorphic and shows strong differences in enzymatic activity among genotypes. At the Outpatient Department for Infertility, University of Rome La Sapienza, we investigated the effect of high-activity ACP1 genotype on spermatic parameters in 105 subjects referred to for varicocele. ACP1 genotype was determined by DNA analysis. In ACP1 *B/*C genotype, which shows the highest enzymatic activity, spermatic concentration is significantly lower and atypical spermatozoa are significantly more frequent as compared to other ACP1 genotypes. It is concluded that subjects carrying *B/*C genotype who represent about 10% of the population have a severe impairment of spermatic parameters in the presence of varicocele.
Subject(s)
Infertility, Male/genetics , Protein Tyrosine Phosphatases/genetics , Proto-Oncogene Proteins/genetics , Spermatozoa/physiology , Varicocele/genetics , Adult , Genotype , Humans , Male , Polymorphism, Single Nucleotide , Receptors, Platelet-Derived Growth Factor/metabolismSubject(s)
Adenosine Deaminase/metabolism , Alkaline Phosphatase/metabolism , Coronary Artery Disease/enzymology , Diabetes Mellitus, Type 2/enzymology , Adenosine Deaminase/genetics , Adult , Alkaline Phosphatase/genetics , Chi-Square Distribution , Coronary Artery Disease/genetics , Diabetes Mellitus, Type 2/genetics , Genotype , Humans , Infant, NewbornABSTRACT
AIM: The aim of this paper was to determine the prevalence of isolated left ventricular noncomapction (ILVNC) in a sample of 150 athletes send by sports doctors to the Valmontone Hospital's Cardiology Division in a span of about three years, with particular interest in non-compacted segments evaluation. The prevention of cardiovascular complications occurring during sporting activity requires detection of pathologies most often clinically latent but whose first presentation can be sudden cardiac death. In Italy, the pre-participation screening program comprises family history and personal cardiac history, clinical examination and electrocardiography. Subjects with abnormalities are further investigated by stress test, echocardiography and laboratory investigations, and those with significant abnormalities are disqualified from sports training and competition. ILVNC results in multiple trabeculations in the left ventricular myocardium and it is postulated to be caused by intrauterine arrest of compaction of the myocardial fibres and meshwork, an important process in myocardial development. This cardiomyopathy should be considered one of the structural cardiac abnormalities responsible for sudden cardiac death. METHODS: There were 150 athletes seen in the Cardiology Division from 2007 to 2010 for an echocardiographic evaluation in order to clarify the nature of physical examination and/or electrocardiogram abnormalities. Echocardiographic diagnosis of ILVNC was based on criteria published by Jenni et al., and by Stölberger et al. RESULTS: Twenty-four of the 150 tested resulted positive for ILVNC (16.0%). This high prevalence is justified because it was a population originally selected because of electrocardiographic abnormalities. CONCLUSION: We believe that in case of unspecific ECG findings, it would be useful to perform echocardiographic examination in order to highlight structural defects. We also believe that it is very important to contemplate ILVNC between the causes of sudden death in young competitive athletes.
Subject(s)
Athletes , Isolated Noncompaction of the Ventricular Myocardium/diagnosis , Adolescent , Adult , Child , Child, Preschool , Death, Sudden, Cardiac/prevention & control , Echocardiography , Female , Humans , Male , Young AdultABSTRACT
OBJECTIVE: To investigate the possible effect of clinical and genetic variables on the association between PTPN22 and endometriosis. METHODS: PTPN22, ACP1 and p53 codon 72 genetic polymorphisms and duration of previous pharmacological treatment were studied. The study sample consisted of 132 women hospitalized for endometriosis diagnosed by laparoscopic intervention and histologically confirmed: 359 healthy blood donors were studied as controls. PTPN22, ACP1 and p53 codon 72 genotypes were determined by DNA analysis. Discriminant statistical analysis, logistic regression analysis, chi square of independence, power test and linear correlation were performed using SPSS programs. RESULTS: A significant increase of PTPN22 *T allele in endometriosis is observed in women carrying ACP1*C allele, in women carrying p53 codon 72 *Pro allele and in women with prolonged pharmacological treatment. CONCLUSIONS: PTPN22 may not be a primary factor in the etiology of endometriosis but may cooperate with clinical and genetic factors influencing susceptibility and clinical course of disease. These new observations point to a multifactorial origin of endometriosis and help to explain the reported differences between human populations concerning the association between PTPN22 and endometriosis.
Subject(s)
Endometriosis/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Protein Tyrosine Phosphatases/genetics , Proto-Oncogene Proteins/genetics , Tumor Suppressor Protein p53/genetics , Adult , Alleles , Female , Humans , Polymorphism, GeneticABSTRACT
OBJECTIVES: Recently, it has been shown that PTPN22 genetic polymorphism is associated with phenotypes related to the risk of atherosclerosis. In the present note, we have searched for a possible association of PTPN22 polymorphism with coronary artery disease (CAD). METHODS: One hundred and thirty-four non-diabetic subjects admitted to hospital for CAD and 174 healthy subjects (blood donors) were studied. PTPN22 genotypes were determined by DNA analysis. Statistical analyses were performed by SPSS programs. RESULTS: In CAD patients, the proportion of carriers of the *T allele of PTPN22 is significantly higher compared to healthy controls (OR 2.66; 95% CI 1.07-6.72). CONCLUSIONS: The present observation confirms the association of PTPN22 phenotype with atherosclerosis and suggests a role of immune mechanism in the pathogenesis of CAD.
Subject(s)
Coronary Artery Disease/genetics , Polymorphism, Genetic , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , PhenotypeABSTRACT
Two hundred and eighty six subjects with cardiovascular diseases and 147 healthy newborns were studied. P53 codon 72 polymorphism was determined by DNA analysis. The association between BMI and diabetes depends on p53 polymorphism: Odds Ratio shows a high significant association between BMI and diabetes in *Arg/*Arg subjects (p=0.00001). No significant association is observed in *Pro allele carriers (p=0.203).
Subject(s)
Cardiovascular Diseases/genetics , Diabetes Mellitus, Type 2/genetics , Genes, p53/genetics , Genetic Predisposition to Disease , Overweight/genetics , Polymorphism, Genetic , Aged , Body Mass Index , Cardiovascular Diseases/complications , Codon , Diabetes Mellitus, Type 2/complications , Female , Humans , Infant, Newborn , Male , Middle AgedABSTRACT
OBJECTIVES: We recently reported an association between the PTPN22 genetic polymorphism and coronary artery disease (CAD) in nondiabetic subjects. Since recent studies suggest that p53 may be involved in coronary atherosclerosis, we have investigated a possible interaction between PTPN22 and p53 codon 72 genetic polymorphisms regarding their effects on susceptibility to CAD in nondiabetic subjects. METHODS: The genotypes of p53 codon 72 and PTPN22 were determined by DNA analysis in 128 nondiabetic subjects with CAD, 122 healthy blood donors and 117 nondiabetic subjects with cardiovascular diseases without CAD. RESULTS: In subjects with the *Arg/*Arg genotype of p53 codon 72, no association was observed between CAD and PTPN22. However, this association was very strong in subjects carrying the *Pro allele of p53 codon 72. Subjects carrying both the *T allele of PTPN22 and the *Pro allele of p53 were overrepresented in CAD nondiabetic cases relative to the other two groups (p = 0.001). CONCLUSIONS: Since both p53 and PTPN22 are involved in autoimmune inflammation, an interaction between the two systems appears biologically plausible. In the analysis of multifactorial disorders, the simultaneous analysis of multiple genes functionally related to diseases will provide a more productive approach than studies of single genetic factors performed from a Mendelian perspective.
Subject(s)
Coronary Artery Disease/genetics , Genes, p53/genetics , Polymorphism, Genetic/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Adult , Alleles , Codon/genetics , Genetic Predisposition to Disease/genetics , Genotype , HumansABSTRACT
Recent investigations suggest that Adenosine Deaminase (ADA) could play a role in susceptibility to rheumatoid arthritis (RA). The purpose of our study is to investigate the possible role of genetic variability of ADA in the susceptibility to RA. We studied three intragenic ADA polymorphisms, ADA1, ADA2 and ADA6, in a sample of 91 subjects with RA and in 246 healthy subjects from the same Caucasian population and compared genotype and pairwise haplotype distributions between cases and controls. No statistically significant differences between RA and controls are observed for ADA genotypes. A border line difference for ADA1-ADA2 haplotype distribution is observed due to a decreased proportion of ADA1 *2/ADA2 *2 haplotype in RA compared to controls. Our data indicate a border line effect of ADA gene polymorphism on susceptibility to RA that need to be confirmed in other clinical settings.
Subject(s)
Adenosine Deaminase/genetics , Arthritis, Rheumatoid/genetics , Alleles , Amino Acid Substitution , Arthritis, Rheumatoid/epidemiology , Codon/genetics , DNA/genetics , DNA Primers , Exons/genetics , Female , Genotype , Haplotypes , Humans , Male , Middle Aged , Polymorphism, Genetic/genetics , Reverse Transcriptase Polymerase Chain Reaction , Rome/epidemiologyABSTRACT
Adenosine inhibits the immune response in tumors. Adenosine deaminase (ADA) controls adenosine level and as ecto-enzyme acts as costimulatory molecule of adenosine receptors and/or CD26. We examined ADA1, ADA2, ADA6 polymorphic sites of ADA gene in 109 subjects with colon cancer from Rome's population and in 246 blood donors as controls from the same population. In colon cancer ADA1*2/ADA2*1 haplotype is more represented, while ADA1*2/ADA2*2 is less represented than in controls. ADA2*2/ADA6*2 is less represented in patients than in controls. Polymorphic sites of ADA might influence cell-mediated anti-tumor immune responses controlling adenosine level and extraenzymatic protein functions.
Subject(s)
Adenosine Deaminase/genetics , Colonic Neoplasms/genetics , Adenosine/genetics , Adenosine/metabolism , Aged , Colonic Neoplasms/enzymology , Female , Genotype , Humans , Male , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polymorphism, Single NucleotideABSTRACT
BACKGROUND: Adenosine deaminase is a polymorphic enzyme that has an important role in immune functions and in the regulation of intracellular and extracellular concentrations of adenosine and adenosine receptor activity. AIM: To search for possible association of type 1 diabetes mellitus (DM1) with three loci haplotypes (ADA1, ADA2, ADA6) of the adenosine deaminase gene. PATIENTS: One hundred and eighty-nine consecutive children with DM1 from Sassari, Sardinia, and a control sample of 239 children from the same area were studied. METHODS: ADA loci genotypes were determined by DNA analysis. RESULTS: Compared to controls, diabetic boys show a decrease of the 2(2)/6(1) haplotype while diabetic girls show an increase of the same haplotype. This association was replicated in an independent sample from Continental Italy. CONCLUSIONS: The 2(2)/6(1) haplotype may exert a protective action in males but may increase susceptibility to DM1 in females: OR = 0.398, 95% CI 0.16-0.96 for males, and OR = 2.31, 95% CI 1.32-4.06 for females.
Subject(s)
Adenosine Deaminase/genetics , Diabetes Mellitus, Type 1/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Child , DNA Mutational Analysis , Female , Gene Frequency , Genetic Association Studies , Genotype , Haplotypes , Humans , Italy , Male , Sex CharacteristicsSubject(s)
Diabetes Mellitus, Type 1/genetics , Genes, p53 , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Age of Onset , Apoptosis/genetics , Child , Codon , Diabetes Mellitus, Type 1/epidemiology , Gene Frequency , Genetic Association Studies , Humans , Italy , Polymorphism, Restriction Fragment Length , Tumor Suppressor Protein p53/chemistry , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/physiologyABSTRACT
Previous published studies have identified a class of women, Normal Weight Obese women (NWO) with normal BMI and high fat content. An important role of Interleukin-15 (IL-15) has been documented in facilitating muscle proliferation and promoting fat depletion. Indeed the presence of three types of IL-15 receptor subunits in fat tissue suggests a direct effect on adipose tissue. We studied three single nucleotide polymorphisms (SNP) of IL-15R-alpha receptor gene and investigated their relationship with NWO phenotype. We considered two classes of women according to their BMI and percent fat mass (percent FAT), class 1: including 72 overweight-obese women (high BMI-high fat mass) and class 2: including 36 NWO (normal BMI, high fat mass). Three sites of Interleukin-15 receptor subunit á gene were examined, located respectively in exon4, exon5 intron-exon border and exon7. Genotyping of the identified polymorphisms was performed by restriction fragment length polymorphism. Haplotype frequency estimation was performed by using the Mendel-University of Chicago program. Odds ratio analyses were calculated by EPISTAT program. Highly significant differences were observed for exon 7- exon5 intron-exon border and exon 4-exon 7 haplotype distribution between class 1 and class 2 women. These results strongly support the hypothesis that genetic variability of the IL-15 receptor has an important role in body fat composition. Our data underscore previous findings that suggest a potential role of IL-15 cytokine in NWO syndrome.
Subject(s)
Body Weight/physiology , Interleukin-15 Receptor alpha Subunit/genetics , Obesity/genetics , Polymorphism, Single Nucleotide , Adult , Body Mass Index , Exons , Female , Haplotypes , Humans , Interleukin-15/genetics , Middle Aged , SyndromeABSTRACT
OBJECTIVES: Assuming an immune component in the pathogenesis of atherosclerosis, we have investigated a possible association between coronary artery disease (CAD) and the acid phosphatase locus 1 (ACP1) genetic polymorphism, which has previously been found to be associated with immune disorders. METHODS: 226 subjects admitted to the hospital for CAD, 358 consecutive newborn infants, 279 adult subjects with type 2 diabetes without CAD and 137 adults without diabetes and without CAD from the Caucasian population of Rome were studied. The ACP1 genotype was determined by DNA analysis. Statistical analyses were performed using the SPSS package. RESULTS: CAD females showed an excess of ACP1 *A/*C and *B/*C genotypes and a deficiency of ACP1 *B/*B genotype compared to controls, while CAD males did not show significant differences. Among diabetic women the proportion of *C allele carriers was much greater in those with CAD than in those without CAD. This difference was much less evident in nondiabetic women. CONCLUSION: ACP1 may be involved in susceptibility to CAD. Since ACP1 has been found to be associated with immunological diseases, our observation reinforces the notion of an immune component in the pathogenesis of atherosclerosis.
Subject(s)
Coronary Artery Disease/epidemiology , Coronary Artery Disease/genetics , Protein Tyrosine Phosphatases/genetics , Proto-Oncogene Proteins/genetics , White People/genetics , White People/statistics & numerical data , Aged , Coronary Artery Disease/immunology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/immunology , Female , Gene Frequency , Genetic Predisposition to Disease/epidemiology , Genotype , Humans , Infant, Newborn , Male , Middle Aged , Polymorphism, Genetic , Risk Factors , Rome/epidemiology , Sex DistributionABSTRACT
An inverse relationship between birth weight and coronary artery diseases is well documented but it remains unclear which exposure in early life might underlie such association. Recently it has been reported an association between adenosine deaminase genetic polymorphism and coronary artery diseases. Gender differences in the degree of this association have been also observed. These observations prompted us to study the possible joint effects of BW, ADA, and gender on the susceptibility to coronary artery diseases. 222 subjects admitted to hospital for nonfatal coronary artery diseases, and 762 healthy consecutive newborns were studied. ADA genotypes were determined by DNA analysis. A highly significant complex relationship has emerged among ADA, birth weight, and gender concerning their role on susceptibility to coronary artery diseases in adult life. Odds ratio analysis suggests that low birth weight is more important in females than in males. ADA( *)2 allele appears protective in males, while in females such effect is obscured by birth weight.
Subject(s)
Colonic Neoplasms/genetics , Isoenzymes/genetics , Neoplasm Proteins/genetics , Polymorphism, Genetic , Protein Tyrosine Phosphatases/genetics , Proto-Oncogene Proteins/genetics , Blood Donors , Colonic Neoplasms/mortality , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Isoenzymes/physiology , Protein Tyrosine Phosphatases/physiology , Proto-Oncogene Proteins/physiologyABSTRACT
The missense PTPN22 C1858T polymorphism recently emerged as an important population-independent risk factor for type 1 diabetes (T1D) and other autoimmune diseases. The PTPN22 gene encodes the lymphoid tyrosine phosphatase (LYP), a negative regulator of signal transduction through the T-cell receptor. Although the frequency of the polymorphism is variable among different ethnic groups, the association between PTPN22 *T1858 and T1D has been replicated in several populations. Here, we contribute the first replication of the association between PTPN22 and T1D in populations from continental Italy, carried out in two independent samples of T1D patients (N = 216 and 82) and controls (N = 271 and 89). Our data also suggest that T1D carriers of the *T1858 allele could be at increased risk for other comorbid autoimmune disorders.