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Biomedical subjects

N Santoro

Publications and source records attributed to N Santoro.

At least 19 recordsLinked to original sources
PubMed2006

Mortality from second tumour among long-term survivors of retinoblastoma: a retrospective analysis of the Italian retinoblastoma registry.

Survivors of retinoblastoma (Rb) are at high risk of dying from second malignant tumour. The occurrence of second malignant neoplasm (SMN) and related mortality in a cohort of 1111 cases from the Italian Retinoblastoma Registry was analysed, considering the possible role of both genetic and iatrogenic causes. Rb patients had a greater than 10-fold excess in overall mortality compared with the general population (standardized mortality ratio (SMR) 10.73, 95% CI 9.00-12.80). Their excess risk attributable to cancers other than Rb was 14.93 95% CI 10.38-21.49). Survivors of hereditary Rb had an SMR for all causes of 16.25 (95% CI 13.20-20.00), whereas their SMR for all cancers was 25.72 (95% CI 17.38-38.07). Survivors of unilateral sporadic Rb had an SMR of 4.12 from all cancers (95% CI 1.55-10.98) and a much higher excess for overall mortality (SMR 13.34, 95% CI 10.74-16.56). As expected, survivors of hereditary Rb had higher mortality from cancers of the bone (SMR 391.90, 95% CI 203.90-753.20) and soft tissue (SMR 453.00, 95% CI 203.50-1008.40), small intestine (SMR 1375.50, 95% CI 344.00-5499.70), nasal cavity (SMR 13.71, 95% CI 1.93-97.35) and cancers of the brain and central nervous system (SMR 41.14, 95% CI 13.2-127.55).

Cohort Studies↗
PubMed2006

Adolescents carrying a missense mutation in the CART gene exhibit increased anxiety and depression.

A Leu34Phe mutation in the cocaine- and amphetamine-regulated transcript (CART) gene has been associated with severe early-onset obesity in an affected family. It has been shown that, in a cell culture system, the mutation resulted in altered CART peptide levels, and animal studies suggest that CART is involved in anxiety as well. The availability of the affected family allowed for testing of anxiety and other traits in humans carrying a mutation in CART gene. This study shows that a small group of adolescents with the mutation exhibit higher anxiety and depression scores than control subjects.

Adolescent↗
PubMed2006

Weight loss in obese children carrying the proopiomelanocortin R236G variant.

To acquire more information relative to the course of obesity in conditions of food restriction in subjects carrying mutations in the melanocortin signaling pathway, 710 obese children (mean age: 9.5+/-2.1 yr; mean z-score body mass index: 3.63+/-1.6) were genotyped for the proopiomelanocortin (POMC) R236G substitution, a variant which has been associated to early onset obesity, by restriction fragment length polymorphism (RFLP) analysis. Three children were heterozygotes for the R236G variant (0.4%). One of them had the metabolic syndrome. This variant was not found in 400 controls. The 3 probands followed a hypocaloric balanced diet and, after about 12 months, normalized their weight as well as fat mass and insulin resistance. The patient with the metabolic syndrome reversed this condition. These results show that a) the R236G substitution of POMC gene, although not a major cause of obesity among Italian obese children and adolescents, is associated with early onset obesity, and that b) inherited alterations of the melanocortin signaling pathway, independently of the degree of obesity, do not preclude the possibility to lose weight in mutated individuals following a hypocaloric diet.

Adolescent↗
PubMed2006

Increased serum lipids are associated with higher CD4 lymphocyte count in HIV-infected women.

OBJECTIVE: Highly active antiretroviral therapy (HAART) has been associated with dyslipidaemia; however, the roles of immune status and non-HIV-disease risk factors remain unclear. METHODS: A cross-sectional analysis of fasting lipids was carried out for 231 women, of whom 132 were HIV-infected and 99 were uninfected. The concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B (apo B) were measured. CD4 lymphocyte count, hepatitis C status, demographics, diet, and anthropometrics were also assessed. RESULTS: A total of 132 women were HIV-infected [30 were antiretroviral-naive, 68 were on protease inhibitors (PIs), and 34 were on non-PI HAART]. HIV infection was associated with higher triglycerides, lower HDL-C, and, among obese women, higher total cholesterol and LDL-C. Non-PI and PI HAART were each independently associated with higher total cholesterol, LDL-C, and apo B, compared with being ART-naive. Among HIV-infected women, after adjustment for HAART use, women with a CD4 lymphocyte count > or =500 cells/microL had total cholesterol 41.8 mg/dL (P = 0.002) and LDL-C 28.8 mg/dL (P = 0.01) higher, on average, than women with a CD4 count <200 cells/microL. Women with a CD4 count of 200-499 cells/microL had total cholesterol 26.31 mg/dL higher, on average, than those with a CD4 count <200 cells/microL (P = 0.04), although differences in LDL-C did not reach significance (15.51 mg/dL; P = 0.12). A higher CD4 count was also associated with higher apo B (P < 0.001). Active hepatitis C infection was associated with lower total cholesterol, LDL-C, triglycerides, and apo B. CONCLUSIONS: Higher CD4 lymphocyte counts were associated with higher lipid levels, suggesting that immune competence may independently affect the dyslipidaemia seen in the HAART era. In addition, it is important that hepatitis C status be assessed in studies of dyslipidaemia in the HIV-infected population.

Adult↗
PubMed2006

Pubic symphysis sclerosis in psoriatic arthritis. Case report.

Pubic symphysis sclerosis is a very interesting event in psoriatic arthritis (PsA). PsA is a cronical arthritis, associated with psoriasis, classified with seronegative spondyloarthrities. There are 5 clinical PsA patterns: an oligoarticular pattern, characterized by asymmetrical involvement of metacarpophalangeal and interphalangeal joints of hands and feet, as well as ankles and knees; a polyarticular pattern; a pattern characterized by involvement of distal interphalangeal joints; an arthritis mutilans pattern, characterized by acro-osteolysis of distal phalanxes; a pattern with spondylitic involvement. Although pubic involvement in PsA is not described in literature, a lot of authors describe the presence of erosive and/or sclerotic osteitis pubis in seronegative spondyloarthrities, without a more accurate subclassification. In seronegative spondyloarthrities sclerotic involvement of pubic symphysis has been described in patients suffering from ankylosing spondylitis for 5-10 years. A case of pubic symphysis sclerosis, evident on radiographs and detected also by magnetic resonance, which shows also a pattern of oedema and enhancement, with increased signal intensity on pubic symphysis in T2-weighted images, after the contrast agent was injected in the bone marrow, is reported in a woman affected by PsA. Pubic symphysis sclerosis is atypical in PsA and may be considered, by analogy with ankylosing spondylitis, the final result of repairing mechanisms of the previous erosive changes.

Arthritis, Psoriatic↗
PubMed2006

Pathogenesis, clinical findings and management of acute and chronic gout.

Gout is a chronic metabolic disease caused by a disorder of the purine metabolism leading to hyperuricaemia. It is determined by the deposition of monosodium urate crystals in joints and other tissues which causes an acute inflammatory response and can induce a permanent tissue damage which defines the urate chronic joint disease which is characterised by the appearance of ulceration of the joint cartilage, marginal osteophytosis, geodic and erosive lesions and chronic inflammation of synovial membrane. Gout and hyperuricaemia usually occur after the age of 30 years and more frequently in men. Hyperuricaemia is the result of an increased production of uric acid or its hypoexcretion by the kidneys, or both. In the pathogenesis of gout and hyperuricaemia are involved genetic and environmental factors; further, different pathologic condition such as glycogenosis, renal insufficiency, use of some drugs, are associated with gout. Treatment of acute gout includes colchicine, nonsteroidal anti-inflammatory drugs and glucocorticoids, whereas in the intercritical periods colchicine is effective for preventive purposes. Urate-lowering therapy with xanthine-oxidase inhibitors or uricosuric agents is indicate only in patients with more than two gout crisis per year, tophaceous deposits, uric acid nephrolithiasis, and interstitial renal disease, as asymptomatic hyperuricaemia does not requires any treatment but can be controlled with preventive dietetic measures and changes in lifestyle.

Acute Disease↗
PubMed2005

Prevalence and clinical implications of bone marrow involvement in pediatric anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) harbors the reciprocal chromosomal translocation t(2;5)(p23;q35) in approximately 80% of the cases. The genes involved are nucleophosmin (NPM) and anaplastic lymphoma kinase (ALK) and the resulting chimeric NPM-ALK protein is thought to play a key role in the pathogenesis of t(2;5) positive ALCL. Few data on bone marrow (BM) involvement in ALCL have been published and they mostly rely on morphological examination of BM smears. We studied 52 ALCL for NPM-ALK expression by RT-PCR: 47/52 biopsies were positive. In 41 of the 47 cases we obtained the BM at diagnosis and investigated the prevalence of minimal BM infiltration by RT-PCR and real-time PCR. Minimal disseminated disease was positive in 25/41 patients (61%), of whom six had morphologically infiltrated BM. Survival analysis demonstrated a 5-year progression-free survival of 41 +/- 11% for patients with molecularly positive BM vs 100% for patients with negative BM (P = 0.001). These results suggest that minimal BM involvement at diagnosis is a common event in pediatric ALCL and that minimal BM disease monitoring could identify patients at risk of relapse.

Adolescent↗
PubMed2005

KEEPS: The Kronos Early Estrogen Prevention Study.

Observational studies have indicated that hormone therapy given at or after menopause is linked to substantial reduction in cardiovascular disease and its risk factors. Recent findings from the Women's Health Initiative (WHI) clinical trial, however, indicate that combined estrogen plus progestin hormone therapy, as well as estrogen-alone hormone therapy (given to women without a uterus), is ineffective in preventing the new onset of cardiac events in previously healthy late menopausal women. Further, the secondary prevention trial, the Heart and Estrogen/progestin Replacement Study (HERS), also failed to demonstrate any benefit of initiation of hormone therapy in women with established coronary heart disease. In light of these results, a hypothesis has arisen that early initiation of hormone therapy, in women who are at the inception of their menopause, will delay the onset of subclinical cardiovascular disease in women. The rationale that earlier intervention than that performed in the WHI and HERS trials will provide cardiovascular benefit to women is the driving force behind the Kronos Early Estrogen Prevention Study, or KEEPS. KEEPS is a multicenter, 5-year clinical trial that will evaluate the effectiveness of 0.45 mg of conjugated equine estrogens, 50 microg weekly transdermal estradiol (both in combination with cyclic oral, micronized progesterone, 200 mg for 12 days each month), and placebo in preventing progression of carotid intimal medial thickness and the accrual of coronary calcium in women aged 42-58 years who are within 36 months of their final menstrual period. A total of 720 women are planned to be enrolled in 2005, with an anticipated close-out of the trial in 2010. This overview summarizes the recruitment and methodology of the KEEPS trial.

Adult↗
PubMed2004

Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity.

OBJECTIVE: To test whether ghrelin variants could play a role in modulating some aspects of the obese phenotype during childhood. DESIGN: We screened the ghrelin gene in 300 Italian obese children and adolescents (mean age 10.5+/-3.2 y; range 4-19 y) and 200 controls by using the single-strand conformation polymorphism and the restriction fragment length polymoprhism analysis. RESULTS: No mutations were detected with the exception of two previously described polymorphisms, Arg51Gln and Leu72Met. For both variations, allelic frequencies were similar between patients and controls. Interestingly, we showed that the Leu72Met polymorphism was associated with differences in the age at obesity onset. Patients with the Met72 allele became obese earlier than homozygous patients for the wild Leu72 allele. The logrank test comparing the plots of the complement of Kaplan-Meier estimates between the two groups of patients was statistically significant (P<0.0001). CONCLUSION: It is unlikely that ghrelin variations cause the obesity due to single-gene mutations. The Leu72Met polymorphism of the ghrelin gene seems to play a role in anticipating the onset of obesity among children suggesting, therefore, that ghrelin may be involved in the pathophysiology of human adiposity.

Adolescent↗
PubMed2003

Premature menopause in a multi-ethnic population study of the menopause transition.

BACKGROUND: Premature menopause, also termed premature ovarian failure (POF), is characterized by cessation of menstruation before the age of 40 years. Little information is available on the general prevalence of POF or on the prevalence by ethnic group. There is also a lack of information on the association of POF with health indicators. METHODS: A cross-sectional survey of women aged 40-55 years was conducted at seven sites in the USA to determine eligibility for a community-based, multi-ethnic longitudinal study of the peri-menopause (The Study of Women Across the Nation, SWAN). Interview data were used to (i). determine the prevalence of self-reported POF overall and by ethnic group, and (ii). assess the association of POF with selected self-reported variables related to health. Cases of POF included only women with no discernible cause for POF. RESULTS: POF was reported by 1.1% (126/11 652) of women. By ethnicity, 1.0% (95% CI, 0.7-1.4) of Caucasian, 1.4% (95% CI, 1.0-2.1) of African American, 1.4% (95% CI, 0.8-2.5) of Hispanic, 0.5% (95% CI, 0.1-1.9) of Chinese and 0.1% (95% CI, 0.02-1.1) of Japanese women experienced POF. The differences in frequency across ethnic groups were statistically significant (P = 0.01). Only Caucasian, African American and Hispanic women were included in further analyses since too few Asian women had POF. In a multivariate model, POF was independently associated with osteoporosis, female hormone use (excluding oral contraceptives), higher body mass index (BMI) and current smoking after adjustment for education level, ability to pay for basics, site and age at interview. In Caucasian women, use of female hormones, osteoporosis, severe disability and smoking were significantly associated with POF. In contrast, POF in African American women was associated with higher BMI and female hormone use, but not osteoporosis. CONCLUSIONS: The prevalence of POF appears to vary by ethnicity. Health factors associated with POF also vary by ethnicity but because of the cross-sectional study design, it is not possible to determine cause and effect relationships. Health risks of POF would benefit from further study.

Adult↗
PubMed2003

Mechanisms of premature ovarian failure.

The median age at menopause in Western populations of women is approximately 51 years. While very late (i.e., after 54 years) menopause is exceedingly uncommon, a sizeable minority of women experience cessation of ovarian function at or prior to age 45. By convention, menopause that occurs at ages 40-45 is considered "early" and occurs in about 5% of women. Premature ovarian failure (POF) is reserved for the approximately 1% of women who experience hypergonadotropic amenorrhea prior to age 40 years. POF represents the end stage of a variety of disorders that result in the loss of ovarian follicles. Depending upon the age at diagnosis, the probability of a genetic, autoimmune, or idiopathic cause will be more or less likely. Two functioning X chromosomes appear necessary for normal ovarian function. The most obvious genetic cause of POF is Turner Syndrome, in which a complete or near-complete loss of the second X chromosome occurs. Turner Syndrome typically results in the most severe and irreversible POF, often clinically evident prior to menarche. Typically, in Turner Syndrome, menopause precedes menarche, and there is no evidence of ovarian function. However, cases with multiple tissues diagnosed as 45, X have been reported to result in ovarian function and even pregnancy. It is likely that mitigating factors, perhaps autosomal, can modify this most severe and irreversible cause of ovarian failure. Lesser degrees of ovarian failure have also been attributed to partial X chromosome deletions and milder degrees of X chromosome mosaicism. Fragile X syndrome is another example of mild POF that can be linked to disorders of the X chromosome. Other genetic defects are believed to cause POF, yet their prevalence has been difficult to determine. The localization of the gene for the blepharophimosis/ptosis/POF Syndrome has been recently reported, yet this finding has not been seen commonly in POF. Other genetic syndromes including POF await elucidation. Many transgenic "knock-out" animals have been created with deficient ovarian function. Most interesting along these lines is the heterozygous FSH receptor knock-out, which exhibits a reduced follicle reserve and early ovarian depletion. Application of this knowledge and translation of these transgenic experiments into elucidation of clinical disease has been difficult, but represents an area of tremendous potential progress in the understanding of the pathogenesis of POF. Another approach to the genetics of POF has been to examine the genome of affected and unaffected individuals. The genetics appear to differ greatly depending upon the timing of the expression of the POF. For example, women with early menopause are more likely to possess the PVUII polymorphic allele for estrogen receptor alpha. Whether or not this polymorph is more common in women with earlier menopause, i.e., POF, is unclear. Pedigree data indicate that early menopause and premature menopause sort similarly within families. The only difference between women with true POF and those with early menopause may be in the timing of the expression of the syndrome, and not in the genetics. Population genetic approaches analyzing affected and unaffected individuals are underway in several research centers and represent another area of progress. Immune and other, idiopathic causes of POF await further clarification. It is clear that this is an area of great research potential. Understanding how ovaries fail may assist women with this disorder by facilitating the development of novel therapies. Additionally, such information will provide important clues about optimizing ovarian function in individuals without POF who are seeking extension of their reproductive life spans or fertility enhancement by other means.

Adult↗
PubMed2002

Assessing menstrual cycles with urinary hormone assays.

The Study of Women's Health Across the Nation (SWAN) is a multiethnic cohort study of middle-aged women enrolled at seven US sites. A subset of 848 women completed a substudy in which their urinary gonadotropins and sex steroid metabolites were assessed during one complete menstrual cycle or up to 50 consecutive days. Urine was analyzed for LH, FSH, estrone conjugates (E1c), and pregnanediol glucuronide (Pdg). To prepare for serial analysis of this large, longitudinal database in a population of reproductively aging women, we examined the performance of algorithms designed to identify features of the normal menstrual cycle in midreproductive life. Algorithms were based on existing methods and were compared with a "gold standard" of ratings of trained observers on a subset of 396 cycles from the first collection of Daily Hormone Substudy samples. In evaluating luteal status, overall agreement between and within raters was high. Only 17 of the 396 cycles evaluated were considered indeterminate. Of the 328 cycles rated as containing evidence of luteal activity (ELA), 320 were considered ELA by use of a Pdg threshold detection algorithm. Of 51 cycles that were rated as no evidence of luteal activity, only 2 were identified by this algorithm as ELA. Evaluation of the day of the luteal transition with methods that detected a change in the ratio of E1c to Pdg provided 85-92% agreement for day of the luteal transition within 3 days of the raters. Adding further conditions to the algorithm increased agreement only slightly, by 1-8%. We conclude that reliable, robust, and relatively simple objective methods of evaluation of the probability and timing of ovulation can be used with urinary hormonal assays in early perimenopausal women.

Algorithms↗
PubMed2002

Successful treatment of Griscelli syndrome with unrelated donor allogeneic hematopoietic stem cell transplantation.

Griscelli syndrome (GS) is a rare autosomal recessive disorder, characterized by pigmentary dilution of the skin and hair and in most patients by abnormal regulation of the immune system, which results in a syndrome of macrophage hyperactivation, known as hemophagocytic lymophohistiocytosis (HLH). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment available for genetically induced HLH. Few cases of successful HSCT from a compatible donor have been reported in children with GS. We describe the first patient with GS cured with an allograft from a compatible unrelated bone marrow donor. We used a novel preparative regimen consisting of busulfan, thiotepa and fludarabine. The demonstrated curative effect of HSCT from an unrelated donor in a patient with genetically determined HLH also supports the use of a systematic diagnostic approach in these patients, in order to identify those with a worse prognosis and needing an urgent allograft in a timely manner.

Bone Marrow Transplantation↗
PubMed2002

Low frequency of melanocortin-4 receptor (MC4R) mutations in a Mediterranean population with early-onset obesity.

BACKGROUND: Melanocortin-4 receptor (MC4R) mutations have been reported as the most common single genetic cause of obesity in some populations and it has been suggested that they may be responsible for more than 4% of early-onset obesity. OBJECTIVES: To verify the presence of mutations of the MC4R coding region in children from southern Italy with early-onset obesity. SUBJECTS AND METHODS: Two-hundred and eight unrelated obese children and adolescents were included in the study. The average age at obesity onset was 4.5+/-2.6 y. MC4R coding region was screened using both single-strand conformation polymorphism (SSCP) analysis and denaturing high-performance liquid chromatography (DHPLC). Automatic sequencing of PCR products of all individuals that showed an aberrant SSCP and/or DHPLC pattern was performed. RESULTS: One novel missense mutation and one previously described polymorphism (Vall03Ile) were identified. The missense mutation C142T, resulting in the substitution of proline with serine at codon 48, within the first MC4R transmembrane domain, was detected at the heterozygous state in a 15-y-old obese girl (body mass index (BMI)=35 kg/m(2)) who has been obese since she was 8 y old. The mutation co-segregated with the obesity phenotype for over three generations and was not found in the control population. CONCLUSIONS: Our data show MC4R obesity causing mutations in less than 0.5% of the patients (ie 1 out of 208 patients) and therefore indicate a low prevalence of MC4R variants in the obese population from southern Italy. The specific genetic background of the Mediterranean population could make it difficult for MC4R mutations to produce an essentially polygenic trait such as common obesity, at least during childhood.

Adolescent↗
PubMed2002

Inadequate leptin level negatively affects body fat loss during a weight reduction programme for childhood obesity.

UNLABELLED: Obesity is a typical example of a complex multifactorial disease arising from behavioural, environmental and genetic factors that may affect individual responses to dietary intake and physical activity. Observational, longitudinal dietary interventional studies in obese patients present contrasting reports on the predictive value of baseline leptin levels. We report on the effect of a weight reduction programme in three different groups of obese children (82 patients in all) assembled on the basis of their baseline leptin levels adjusted for body mass index (BMI), gender and pubertal development. The effectiveness of this programme was decreased in patients with relative hyperleptinaemia or hypoleptinaemia compared to children with baseline leptin levels appropriate to BMI gender and pubertal development. CONCLUSION: Information gained from leptin assays could provide predictive insight into an individual's ability to lose body fat and may therefore have important implications for our approach to the treatment and prevention of childhood obesity.

Adolescent↗
PubMed2001

Effect of protracted high-dose L-asparaginase given as a second exposure in a Berlin-Frankfurt-Münster-based treatment: results of the randomized 9102 intermediate-risk childhood acute lymphoblastic leukemia study--a report from the Associazione Italiana Ematologia Oncologia Pediatrica.

PURPOSE: To assess in a randomized study the therapeutic effect of the addition of high-dose L-asparaginase (HD ASP) in the context of a Berlin-Frankfurt-Münster (BFM)-based chemotherapy regimen for intermediate risk (IR) childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From March 1991 to April 1995, a total of 705 patients, with 59% of the cohort of patients fewer than 15 years old, with newly diagnosed non-B ALL, enrolled onto the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) ALL-91 study, were assigned to the IR group. Patients in remission at the beginning of the reinduction phase were randomized either to the standard treatment (SD ASP arm) or the experimental treatment (HD ASP arm; weekly intramuscular administration of HD ASP 25,000 IU/m(2) repeated for a total of 20 weeks). Most of the patients (90%) were treated with Erwinia chrysanthemi L-asparaginase product. RESULTS: Among the 610 patients randomized to the SD ASP arm (n = 322) or to the HD ASP arm (n = 288), relapse occurred at a median time of 24 months after randomization in 76 (24%) and in 64 children (22%), respectively. Most of the relapses occurred in the marrow (100 isolated, 21 combined). There was no significant difference between the disease-free survival in the two treatment arms (P =.64), with estimated values at 7 years from randomization of 72.4% (SE 3.1) v 75.7% (SE 2.6) in the SD ASP and HD ASP arms, respectively. CONCLUSION: No advantage was observed for IR ALL children treated with BFM-based intensive chemotherapy who received protracted E chrysanthemi HD ASP during reinduction and the early continuation phase.

Adolescent↗
PubMed2001

Molecular screening of the proopiomelanocortin (POMC ) gene in Italian obese children: report of three new mutations.

BACKGROUND: Although linkage studies strongly suggest that proopiomelanocortin (POMC) alterations could play a role in the genetic predisposition to obesity, systematic POMC mutational analysis did not completely confirm this hypothesis. OBJECTIVES: To verify the presence of mutations of the POMC coding region in Italian children with very early onset obesity. SUBJECTS AND METHODS: Eighty seven unrelated Italian obese children and adolescents were studied. Mean age at obesity onset was 4.7+/-2.5 y. The POMC gene coding region was screened using single-strand conformation polymorphism (SSCP) analysis. Bi-directional automatic sequencing of PCR products was performed for all individuals who showed an aberrant SSCP pattern. RESULTS: Three new mutations have been identified in the heterozygous state in three patients: (a) G3834C, resulting in the substitution of Ser with Thr at codon 7 within the POMC signal peptide; (b) C3840T, resulting in the substitution of Ser with Leu at codon 9 of the pre-proopiomelanocortin signal peptide; and (c) C7406G, producing the substitution of Arg with Gly at codon 236 within the beta-endorphin peptide. A polymorphism consisting of a 9 bp insertion, AGC AGC CGC, between position 6997 and 6998 has been found at the heterozygous state in nine patients. They showed leptin levels adjusted for BMI, gender and pubertal stage significantly higher than obese subjects homozyous for the POMC wild-type allele. CONCLUSIONS: Mutations in codons 7 and 9 of the signal peptide may alter the translocation of the pre-proopiomelanocortin into the endoplasmic reticulum and, therefore, can be implicated in obesity. Although further studies are required, the polymorphism between position 6997 and 6998 may represent one of the genetic variations that explain the linkage between obesity and POMC. International Journal of Obesity (2001) 25, 61-67

Adolescent↗