Italian Caucasians Research Articles

A pilot study evaluating the contribution of SLC19A1 (RFC-1) 80G>a polymorphism to Alzheimer's disease in Italian Caucasians.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and the primary form of dementia in the elderly. Polymorphisms of genes involved in folate metabolism have been frequently suggested as risk factors for sporadic AD. A common c.80G>A polymorphism (rs1051266) in the gene coding for the reduced folate carrier (SLC19A1 gene, commonly known as RFC-1 gene) was investigated as AD risk factor in Asian populations, yielding conflicting results. We screened a Caucasian population of Italian origin composed of 192 sporadic AD patients and 186 healthy matched controls, for the presence of the RFC-1 c.80G>A polymorphism, and searched for correlation with circulating levels of folate, homocysteine, and vitamin B12. No difference in the distribution of allele and genotype frequencies was observed between AD patients and controls. No correlation was observed among the genotypes generated by the RFC-1 c.80G>A polymorphism and circulating levels of folate, homocysteine, and vitamin B12 either in the whole cohort of subjects or after stratification into clinical subtypes. Present results do not support a role for the RFC-1 c.80G>A polymorphism as independent risk factor for sporadic AD in Italian Caucasians.

TNF-α, IL-4Rα AND IL-4 Polymorphisms in Mild to Severe Asthma from Italian Caucasians

Asthma is a chronic airway inflammatory disease associated with airway hyperresponsiveness which affects subjects with genetic predisposition. An association has been reported between some polymorphisms in various cytokine genes and asthma. Most of them are single nucleotide polymorphisms (SNPs). These polymorphisms are detected in the protein coding sequence or in the promoter region thus influencing cytokine production. We investigated the involvement of SNP mapping in 5 cytokine genes in mild to severe asthmatics of Italian Caucasians. The frequency of alleles and genotypes, relatively to 10 allelic specificities of the cytokine genes, was defined in 57 asthmatics and in 124 control subjects by a Polymerase Chain Reaction-Sequence Specific Primer method. TNF-alpha -308A and TNF-alpha -238A allele frequencies were higher in asthmatics than in controls (p less than 0.001). Significant differences in the frequency of IL-4 -590T allele and of IL-4Ralpha +1902A allele were also detected in asthmatics in comparison with controls (pless than 0.001 and p=0.005, respectively). Similarly, IL-1alpha -889C allele was present in 84.1 percent of asthmatics and in 70.2 percent of controls (p=0.013). Furthermore, the IL-4Ralpha +1902A/A and IL-1alpha -889C/C homozygous conditions and the TNF-alpha -308G/A, TNF-alpha -238G/A, IL-4 -590T/C and IL-10 -1082G/A heterozygous conditions were significantly associated with asthma (p less than 0.05). ACA haplotype of IL-10 was observed only in asthmatic patients. This study reports, for the first time, the frequency of 10 different single nucleotide polymorphisms in 5 cytokine genes in the Italian Caucasians. Furthermore, we also indicate that in our population some single nucleotide polymorphisms are associated with mild to severe bronchial asthma.

Comparison of A1C, fasting and 2-h post-load plasma glucose criteria to diagnose diabetes in Italian Caucasians

Background and aimsThe American Diabetes Association (ADA) has revised criteria for diagnosis of type 2 diabetes recommending an A1C cut point of ≥6.5% in addition to criteria based on glucose levels. We compared A1C, fasting plasma glucose (FPG) or 2-h post-challenge glucose (2-hPG) criteria for the diagnosis of diabetes in a cohort of Italian Caucasians. Methods and resultsA total of 1019 individuals without known diabetes completed an oral glucose tolerance test (OGTT) and had A1C measured. Moderate agreement existed for A1C and FPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.522), with 85.5% of individuals classified as not having diabetes by both A1C and FPG criteria, and 5.8% classified as having diabetes by both A1C and FPG criteria. Discordant classifications occurred for 5.5% of individuals who had an A1C ≥ 6.5% and FPG <126 mg dl−1, and for 3.2% who had an A1C <6.5% and FPG ≥126 mg dl−1. Modest agreement existed for A1C and 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.427), with 81.8% of individuals classified as not having diabetes by both A1C and 2-hPG criteria, and 6.0% classified as having diabetes by both A1C and 2-hPG criteria. The area under the receiver operating characteristic curve of A1C for identifying subjects with diabetes according to FPG or 2-hPG criteria was 0.856 and 0.794, respectively. Modest agreement existed for A1C and FPG and/or 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.446). ConclusionsA1C ≥ 6.5% demonstrates a moderate agreement with fasting glucose and 2-hPG for diagnosing diabetes among adult Italian Caucasians subjects.

Risk Profiles in Type 2 Diabetes (Metabolic Syndrome): Integration of IL-10 Polymorphisms and Laboratory Parameters to Identify Vascular Damages Related Complications

Recently it has been reported that low serum IL-10 levels are associated with an increased susceptibility for metabolic syndrome and type 2 diabetes mellitus (T2DM). We investigated whether the -1087G/A (rs1800896), -824C/T (rs1800871), -597C/A (rs1800872) IL-10 polymorphisms were associated with type 2 diabetes in a study on a cohort of Italian Caucasians comprising 490 type 2 diabetic and 349 control subjects. Stratifying the data according to IL-10 genotypes, trends for the progressive increase of glucose and neutrophil levels were observed in -1087GG vs. -1087GA vs. -1087AA positive diabetic patients (-1087GG<-1087GA<-1087AA). In addition, evaluating the laboratory parameters according to the -597/-824/-1087 derived haplotypes a significant increase of neutrophils was found in diabetic vs. non-diabetic -597A/ -824T/-1087A positive subjects (Student t test = 3.707, p<0.01). In an attempt to integrate clinical laboratory and immunogenetic data to determine whether these factors taken together define sufficient risk sets for type 2 diabetes we performed the grade-of-membership analysis (GoM). GoM allowed to identify a population of subjects negative for IL-10 -824T allele, 74.4% of which were diabetic patients characterised by vascular damages (Chronic kidney failure and/or Myocardial Infarction), reduction of haematocrit, increase of blood urea nitrogen, creatinin and monocyte levels. These data seem to suggest that -597A/-824T/-1087A negative subjects are more prone to the major type 2 diabetic vascular damages and allow to hypothesise that the contemporary evaluation of some simple hematochemical parameters and IL-10 SNPs may allow identifying diabetic patients with the worse prognostic profile, needing both better complication prevention planning and therapeutic strategies.

Impact of lowering the criterion for impaired fasting glucose on identification of individuals with insulin resistance. The GISIR database.

We assessed the accuracy of the American Diabetes Association (ADA)2003 definition of impaired fasting glucose (IFG) in identifying subjects with low insulin sensitivity, and determined cardiovascular risk factors in ADA2003 IFG subjects. This study included 930 non-diabetic Italian Caucasians from the GISIR database in which subjects underwent a hyperinsulinaemic-euglycaemic clamp performed with a standard technique. Low insulin sensitivity was defined as being in the lower quartile of glucose metabolized during the last hour of the clamp (M). Subjects were stratified in the following groups: normal fasting glucose (NFG) (<100 mg/dL), IFG100 (100-109 mg/dL), ADA1997 IFG110 (110-125 mg/dL), and ADA2003 IFG (100-125 mg/dL). The sensitivity of identifying subjects with low insulin sensitivity increased adopting the ADA2003 criterion. After Bonferroni correction for multiple comparisons, both IFG100 and ADA1997 IFG110 showed significantly higher body mass index (BMI), waist, systolic blood pressure (SBP) and diastolic blood pressure (DBP), triglyceride, fasting plasma insulin (FPI) and fasting plasma glucose (FPG), and lower insulin sensitivity as compared with NFG. As compared with IFG100, ADA1997 IFG110 showed significantly higher BMI, waist, SBP, FPI, FPG, and lower insulin sensitivity. ADA2003 IFG group showed significantly higher BMI, waist, SBP and DBP, triglyceride, cholesterol, FPI, and FPG, but lower HDL levels and insulin sensitivity compared with NFG subjects. Although neither the ADA2003 nor the ADA1997 definition of IFG appears to be particularly efficacious for the identification of subjects' low insulin sensitivity, lowering the criterion to the ADA2003 glucose threshold increased the sensitivity without affecting the specificity. ADA2003 IFG showed a worse cardiovascular risk profile compared with NFG.

Metabolically Healthy but Obese Women Have an Intermediate Cardiovascular Risk Profile Between Healthy Nonobese Women and Obese Insulin-Resistant Women

Obesity is associated with metabolic and cardiovascular risk factors that include type 2 diabetes, hypertension, and dyslipidemia (1–4). A subset of obese subjects has been identified that appears to be protected from obesity-related metabolic abnormalities (5–11). These subjects, termed metabolically healthy but obese (MHO), are relatively insulin sensitive and have a rather favorable cardiovascular risk profile (5–11). Although the existence of MHO individuals has been recognized, only a few studies have examined in detail the metabolic characteristics associated with their protective profile (5–13). Whereas MHO individuals appear to have a more favorable cardiovascular risk profile than insulin-resistant obese (IRO) individuals, they show early signs of atherosclerosis compared with lean subjects, which could not be explained by alterations in cardiovascular risk factors (12). Among the factors that may account for the early atherosclerosis, insulin-like growth factor (IGF)-1 is a plausible candidate because low plasma IGF-1 concentrations are associated with type 2 diabetes, insulin resistance (14–16), and increased risk of coronary artery disease (17–22). To further characterize the protective profile of MHO individuals, we compared clinical characteristics, including cardiovascular risk factors, plasma IGF-1 levels, and intima-media thickness (IMT) of the common carotid artery, of a group of MHO women from a cohort of nondiabetic Italian Caucasians with those of two age-matched groups comprising healthy nonobese or …

Metabolic and cardiovascular risk factors in subjects with impaired fasting glucose: the 100 versus 110 mg/dL threshold

In 2003, the American Diabetes Association (ADA) established a new cutoff for impaired fasting glucose (IFG) by reducing it from 110 to 100 mg/dL. This change was challenged as to its appropriateness. A few studies have examined the impact of the ADA(2003) threshold of IFG on metabolic and cardiovascular risk factors. We examined whether metabolic and cardiovascular risk factors, including inflammatory biomarkers, differ in subjects with the new ADA(2003) threshold of IFG (IGF100) as compared with subjects with the old ADA(1997) threshold of IFG (IFG110) in a cohort of 946 nondiabetic Italian Caucasians (fasting plasma glucose < 126 mg/dL). As compared with normal fasting glucose (NFG), subjects with IFG100 and IFG110 had higher body mass index (BMI), waist circumference, total and low density lipoprotein (LDL) cholesterol, triglyceride, fasting and 2-h post-challenge plasma glucose, fasting insulin, systolic blood pressure, and lower levels of high density lipoprotein (HDL) and insulin-like growth factor I (IGF-I). In a logistic regression analysis with adjustment for age and gender, IFG110 was associated with higher risk of post-challenge glucose intolerance as compared with IFG100. As compared with IFG100, subjects with IFG110 have significantly lower levels of circulating IGF-I. As compared with NFG, IFG110, but not IFG100, showed a significant association with increased levels of inflammatory markers including white blood cell count (WBCC), and C-reactive protein (CRP). Both CRP and WBCC were correlated with 2-h plasma glucose but not with fasting plasma glucose (FPG). The data show that IFG110 is associated with a worse metabolic and cardiovascular risk profile as compared with IFG100.

Plasma interleukin‐6 levels are increased in subjects with impaired glucose tolerance but not in those with impaired fasting glucose in a cohort of Italian Caucasians

While the relationship between impaired glucose tolerance (IGT) and circulating interleukin-6 (IL-6) is well established, there is no information whether IL-6 levels are elevated in impaired fasting glucose (IFG). To this end, we examined the relationship between plasma IL-6 concentration and different degrees of glucose homeostasis in a cohort of 470 Italian Caucasian subjects comprising 236 normal glucose tolerant (NGT), 49 IFG, 51 IGT, and 134 type 2 diabetic subjects. We observed that IL-6, CRP and fibrinogen levels were higher in subjects with IGT or type 2 diabetes as compared with NGT and IFG subjects. Univariate correlations between IL-6 concentrations and metabolic variables in the whole cohort showed that IL-6 levels were positively correlated with age, BMI, waist, systolic and diastolic blood pressure, fasting plasma glucose, triglycerides, CRP, fibrinogen, and negatively correlated with insulin sensitivity, IGF-I and HDL. In a subgroup analysis including NGT, IFG and IGT (n = 336), IL-6 levels were positively correlated with age, BMI, waist, systolic and diastolic blood pressure, triglycerides, CRP, fibrinogen, fasting insulin, 2 h post-load glucose, and negatively correlated with insulin sensitivity, IGF-I and HDL. Stepwise linear regression analysis in a model including gender, age, BMI, waist, glucose tolerance status, fasting plasma glucose, 2 h post-load glucose, triglycerides, HDL, fasting insulin, and insulin sensitivity revealed that waist was the only independent variable associated with IL-6 levels accounting for 21.0% of its variation (P < 0.0001). These data show that IGT and type 2 diabetes, but not IFG, are associated with elevated plasma IL-6 levels.

Variants of the Interleukin-10 Promoter Gene Are Associated With Obesity and Insulin Resistance but Not Type 2 Diabetes in Caucasian Italian Subjects

Interleukin (IL)-10 is a major anti-inflammatory cytokine that has been associated with obesity and type 2 diabetes. The three polymorphisms -1082G/A, -819C/T, and -592C/A in the IL10 promoter were reported to influence IL10 transcription. We investigated whether these polymorphisms were associated with type 2 diabetes and related traits in a cohort of Italian Caucasians comprising 551 type 2 diabetic and 1,131 control subjects. The -819C/T and -592C/A polymorphisms were in perfect linkage disequilibrium (r(2) = 1.0). The -1082G/A polymorphism was not associated with type 2 diabetes or related traits. Although the -592C/A polymorphism was not associated with type 2 diabetes, nondiabetic homozygous carriers of the A allele showed increased BMI and insulin resistance and lower plasma IL-10 levels compared with the other genotypes. In the nondiabetic group, the ATA haplotype was associated with an increased risk for obesity (odds ratio 1.28 [95% CI 1.02-1.60]; P = 0.02). The ATA/ATA composite genotype was associated with an increased risk for obesity (1.96 [1.16-3.31]; P = 0.01) and insulin resistance (1.99 [1.12-3.53]; P = 0.01). This study suggests that polymorphisms and haplotypes of the IL10 promoter may be associated with obesity and insulin resistance in a large sample of Italian Caucasians.

CTLA4 gene polymorphism in Italian patients with colorectal adenoma and cancer

Background and aims. Colorectal cancer is a major health problem. Colonoscopic colorectal cancer screening is cumbersome and expensive. Identification of genetic risk of colorectal cancer may help to select the subjects who could benefit from colonoscopy. The immune system plays a fundamental role in the human–environment interaction, and the carcinogenic effects of many environmental factors are mediated by the chronic activation of the immune system in a genetic-controlled fashion. Cytotoxic T lymphocyte associated antigen 4 (CTLA4) plays an inhibitory role in regulating lymphocyte functions. The loss of CTLA4 function is responsible for loss of mucosal lymphocyte tolerance. The G allele at position +49 of exon 1 of the CTLA4 gene affects the CTLA4 function. We evaluated in an association study the role of CTLA4 A+49G polymorphism as a risk factor for colorectal neoplasm. Patients and methods. Five hundred and fifty-six patients (male 295; female 261) who underwent colonoscopy at our Centre were enrolled in the study and divided into three groups: Colorectal cancer (132 patients, M/F 68/64, mean age 66 ± 11 years); Colorectal adenoma (186 patients, M/F 110/76, mean age 65 ± 11 years); Healthy controls (238 patients, M/F 117/121, mean age 63 ± 10 years). DNA was extracted from peripheral blood, CTLA4 gene was amplified by using specific primers, and A+49G polymorphism was analysed by restriction enzyme digestion. Results. No statistically significant differences in the genotype distribution among Control and Adenoma groups ( p = 0.93), Control and Carcinoma groups ( p = 0.52), and Adenoma and Carcinoma groups ( p = 0.53) were observed. Conclusion. There is no significant correlation between CTLA4 A+49G polymorphism and the risk of colorectal neoplasm among Italian Caucasians.

Type 2 diabetes mellitus is becoming the most common type of diabetes in school children

Obesity, now an epidemic in the USA, northern Europe, and Italy, is associated with several co-morbidities that shorten life expectancy, in particular type 2 diabetes mellitus (T2DM), arterial hypertension, and hyperlipidemia. The impact of obesity on mortality is evident in all ages, and is especially strong in young persons. Obesity, especially visceral obesity, associated with a sedentary lifestyle, is among the strongest risk factors for T2DM, and a diagnosis of T2DM seems to increase linearly as a function of duration of obesity. The pathogenesis of T2DM is based on a dual defect, i.e. increased insulin resistance coupled with defective insulin release. The main abnormality in obesity is increased insulin resistance, while insulin release, even though defective compared with body needs, is usually abundant. The incidence of obesity among children aged 6-16 years is now even greater than that among adults: in Italy, figures up to 30% have been reported. As in adults, obesity is a cause, among children, of arterial hypertension, left ventricular hypertrophy, hyperlipidemia, non-alcoholic-steato hepatitis, sleep apnea syndrome (SAS), and orthopedic, psychological, and social problems. Together with an increase in body weight, there is an increase of visceral fat. Obesity in children has also led to a tremendous increase in the prevalence of impaired glucose tolerance (IGT); the percentages span from 25% in a multiethnic cohort in the USA, to 4% in Italian Caucasians. Management of obesity and of T2DM in children has to face the issue of poor compliance; there is consensus that dietary treatment of obese T2DM children is a failure, so that drugs are required; the only drug evaluated in a formal trial is metformin, that behaves in terms of efficacy and of minor side effects as in adults. In conclusion, obesity in children is not pure obesity, but is accompanied by co-morbidities that cluster to form the "metabolic syndrome" just like in the adults. If this epidemics continues and is not properly challenged, in the next decades we will face an epidemic of early cardiovascular morbidity and mortality.

Lack of association between UCP2 gene polymorphisms and obesity phenotype in Italian Caucasians.

The importance of the genetic component on adipose tissue accumulation has been clearly demonstrated. Among the candidate genes investigated, there are those that regulate thermogenesis and, thus, can affect energy expenditure. The uncoupling proteins (UCPs) are a family of proteins that uncouple respiration leading to generation of heat and increased energy expenditure. Contradictory data indicate that allelic variants in their coding genes might be associated with obesity. In this study we evaluated the role of two allelic variants of the UCP2 gene in obesity and the association with its sub-phenotypic characteristics. To this aim, 360 morbidly obese patients [age: 45 +/- 15 yr, body mass index (BMI): 46 +/- 7 kg/m2] and 103 normal weight subjects (BMI < 24 kg/m2) were genotyped for the 45 bais-pair (bp) insertion/deletion (I/D) in the 3'-untraslated region of exon 8 of the UCP2 gene while the presence of an Ala/Val substitution at codon 55 (Ala55Val) of the same gene was studied in 104 obese and 50 lean subjects. Patients also underwent a study protocol including measurements of BMI, waist-to-hip ratio (WHR), resting energy expenditure (REE), energy intake, fat mass (FM) and free fat mass (FFM), total cholesterol (TCH), high density lipoprotein (HDL) cholesterol, triacylglyceroles (TG), leptin levels, basal glucose, immunoreactive insulin (IRI), glycated haemoglobin (HbA1c), insulin sensitivity and thyroid hormones. No significant association between the two polymorphisms studied and the clinical, metabolic and anthropometric parameters characteristic of the obese phenotype was found. These results, in accordance with similar findings previously obtained in other ethnic groups, suggest that these two UCP2 allelic variants may not have a direct role in the pathogenesis and development of obesity.

Allele frequencies of polymorphisms of TNFA, IL-6, IL-10 and IFNG in an Italian Caucasian population.

Polymorphisms in the regulatory and intronic regions of several cytokines have been associated with differential cytokine production. In this paper we genotyped, using the polymerase chain reaction-sequence-specific primers (PCR-SSP) method, a series of 363 healthy Italian Caucasians with the aim of obtaining a reference population for further studies on the role of cytokines in the inflammatory and immune responses. We also compared the results to those for other populations. The polymorphisms analysed were those of tumour necrosis factor alpha (TNFA), interleukin 6 (IL-6), interleukin 10 (IL-10) and interferon gamma (IFNG). We found that the frequency of allele TNFA*1 at position -380 was 87.7% and that of TNFA*2 was 12.4%, significantly different from those of the UK and Japanese populations but not different from that of a population in Gambia. For IL-10 the frequencies of alleles -1082A and -1082G were 63.0% and 37.0% and those of alleles -819C, - 819T, -592C and -592A were 70.8, 29.2, 70.8 and 29.2%, respectively, significantly different from those observed in south-east England, in Manchester and in an Oriental population from southern China. The frequencies of IL-6 alleles - 174C and -174G were 29.0 and 71.0%, respectively; for IFNG polymorphisms at position -874, in the population under evaluation, the alleles -874T and -874A were present in 44.7 and 55.3% of the subjects, respectively. Genotype frequencies of IL-6 were significantly different from those observed in populations from Germany and from the UK. The analysis carried out by our group indicates that there is heterogeneity in the frequencies of the cytokine polymorphisms among the different Caucasian populations, and this underlines the importance of a 'local' reference population when evaluating the clinical relevance of cytokine gene polymorphisms.

Italian population data on two new short tandem repeat loci: D2S1338 and Penta E

A population study on two new short tandem repeat (STR) loci D2S1338 (a tetranucleotide repeat) and Penta E (a pentanucleotide repeat) was performed on 208 unrelated Italian Caucasians. The DNA was amplified by polymerase chain reaction (PCR) and separation and detection of the amplified STR fragments were carried out by use of a PE/ABD PRISM 377 DNA Sequencer 377 automated system (Applied Biosystems Division/Perkin-Elmer). Both loci meet Hardy–Weinberg expectations. There is no evidence for departures from expectations between the two loci. The combined Probability of Discrimination and Probability of Exclusion for the two STR loci are 0.999155 and 0.944925, respectively. The results demonstrate that these two regions can be useful for differentiating among individuals, particularly in concert with other STR loci.

Italian population data on two new short tandem repeat loci: D6S477 and D19S433

A population study on two new short tandem repeat (STR) loci D6S477 and D19S433 was performed on 214 unrelated Italian Caucasians. The DNA was amplified by PCR and separation and detection of the amplified STR fragments were carried out by use of a PE/ABD PRISM ™ 377 DNA sequencer 377 automated system (Applied Biosystems Division/Perkin Elmer). Both loci meet Hardy–Weinberg expectations. There is no evidence for departures from expectations between the two loci. The combined probability of discrimination and probability of exclusion for the two STR loci are 0.997161 and 0.883183, respectively. The results demonstrate that these loci can be useful for human identification in forensic cases in Italy.

Italian population data on thirteen short tandem repeat loci: HUMTH01, D21S11, D18S51, HUMVWFA31, HUMFIBRA, D8S1179, HUMTPOX, HUMCSF1PO, D16S539, D7S820, D13S317, D5S818, D3S1358

A population study on thirteen short tandem repeat (STR) loci was performed on 223 unrelated Italian Caucasians. The DNA was amplified by PCR. Separation and detection of the amplified STR fragments was carried out by use of 377 automated system (Applied Biosystems Division/Perkin Elmer). All loci meet Hardy–Wienberg expectations, and the data show only five departures out of seventy-eight pairwise locus tests which is close to expectations of 5% (5/78=6.4%). When correcting for multiple tests, there is little evidence for departures from expectations between loci. The combined Power of Exclusion for the thirteen STR loci is 0.99999270. The results demonstrate that these loci will be very useful for human identification in forensic cases in Italy.

Italian Population Data on the Polymarker System and on the Five Short Tandem Repeat Loci CSF1PO, TPOX, TH01, F13B, and vWA

A population study on five short tandem repeat (STR) loci and five sequence specific polymorphism loci was performed on unrelated Italian Caucasians. Separation and detection of the amplified STR fragments were carried out by high resolution vertical denaturing polyacrylamide gel electrophoresis (PAGE) and silver staining, respectively. The sequence specific loci were analyzed using the AmpliType PM Typing Kit (Perkin Elmer, Foster City, CA). All loci, except Gc (p = 0.031), meet Hardy-Wienberg expectations. In addition, there is no evidence for association of alleles between pairs of loci. The combined power of discrimination for the five STR loci is 0.9999862 and for the PM loci is 0.99503. The results suggest that these loci may be useful for human identification cases in Italy.