Level of Trace Elements (Copper,Zinc, Magnesium and Selenium) and Toxic Elements (Lead and Mercury) in the Hair and Nail of Children with Autism

Autism is a multi-factorial pathology observed in children with altered levels of essential and elevated levels of toxic elements. There are also studies reporting a decrease in nutritional trace elements in the hair and nail of autistic children with healthy controls; moreover, bioelements have been shown to play an important role in the central nervous system. Therefore, the purpose of the present study was to assess the levels of trace elements like copper (Cu), zinc (Zn), magnesium (Mg), and selenium (Se) and toxic elements like mercury (Hg), and lead (Pb) in the hair and nail samples of autistic children and to evaluate whether the level of these elements could be correlated with the severity of autism. The subjects of the study were 45 autistic children with different grades of severity (low (LFA), medium (MFA), and high (HFA) functioning autism) according to Childhood Autism Rating Scale, n = 15 children in each group and 50 healthy children (age and sex matched). The boys and girls ratio involved in this study was 4:1, and they were 4-12 years of age. The study observed a valid indication of Cu body burden in the autistic children. The children with different grades of autism showed high significance (p < 0.001) in the level of copper in their hair and nail samples when compared to healthy controls. The level of Cu in the autistic children could be correlated with their degree of severity (more the Cu burden severe is autism). The study showed a significant elevation (p < 0.001) in the levels of toxic metals Pb and Hg in both hair and nail samples of autistic children when compared to healthy control group. The elevation was much pronounced in LFA group subjects when compared among autistic groups MFA and HFA. The levels of trace elements Mg and Se were significantly decreased (p < 0.001) in autistic children when compared to control. The trace element Zn showed significant variation in both hair and nails of LFA group children when compared to control group and other study groups. The significant elevation in the concentration of Cu, Pb, and Hg and significant decrease in the concentration of Mg and Se observed in the hair and nail samples of autistic subjects could be well correlated with their degrees of severity.     

Analysis of Hair Trace Elements in Children with Autism Spectrum Disorders and Communication Disorders

The primary objective of the present study is analysis of hair trace elements content in children with communication disorder (CD) and autism spectrum disorder (ASD). A total of 99 children from control, CD, and ASD groups (n = 33) were examined. All children were additionally divided into two subgroups according to age. Hair levels of trace elements were assessed using inductively coupled plasma mass spectrometry. The difference was considered significant at p < 0.01. The obtained data demonstrate that children with CD are characterized by significantly increased hair lithium (Li) (96 %; p = 0.008), selenium (Se) (66 %; p < 0.001), arsenic (As) (96 %; p = 0.005), beryllium (Be) (150 %; p < 0.001), and cadmium (Cd) (72 %; p = 0.007) content, being higher than the respective control values. In the ASD group, hair copper (Cu), iodine (I), and Be levels tended to be lower than the control values. In turn, the scalp hair content of Se significantly exceeded the control values (33 %; p = 0.004), whereas the level of iron (Fe) and aluminum (Al) tended to increase. After gradation for age, the most prominent differences in children with CD were detected in the elder group (5–8 years), whereas in the case of ASD—in the younger group (3–4 years old). Taking into account the role of hair as excretory mechanism for certain elements including the toxic ones, it can be proposed that children suffering from ASD are characterized by more profound alteration of metal handling and excretion in comparison to CD.     

Lead, copper, zinc, and magnesium content in hair of children and young people with some neurological diseases

The lead, copper, zinc, and magnesium levels of scalp hair taken from 153 children aged 1–15 yr and young people (16–18 yr) with selected neurological disorders (hyperexcibility, loss of consciousness, and epileptiform convulsions of an unknown origin, etc.), were measured using the atomic absorption spectrometry method and then compared with a control group of healthy children (n=108). The research indicated significantly reduced mean levels of magnesium in the hair of children suffering from selected neurological diseases (in children aged 11–15 yr of age, above 30%; up to 5 yr of age, nearly 30%; the differences were statistically significant at p<0.05) and slightly decreased mean levels of copper (differences statistically significant at p<0.05, particularly in the 11 to 15-yr category). Differences in zinc levels in hair were inconsiderable (not statistically significant in any age groups). The lead level in the hair of the above-mentioned group of children was exceeded in relation to the control group (a statistically significant difference at p<0.05 for the total group). A more than twofold decrease in the mean value of the Mg/Pb ratio (and a nearly 30% decrease in the value of the Mg/Zn ratio) in the hair of children suffering from neurological diseases suggests that the high toxicity of lead accompanying, among other things, magnesium deficiencies might be a cause of the observed disorders in children.     

Influence of smoking on serum and milk malondialdehyde, superoxide dismutase, glutathione peroxidase, and antioxidant potential levels in mothers at the postpartum seventh day

The aim of the study was to investigate simultaneously serum and milk malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, and antioxidant potential (AOP) in active-smoking, passive-smoking, and nonsmoking mothers and to search if there is any difference between serum and milk oxidant/ antioxidant status caused by smoking. According to their smoking status, 60 mothers (age range: 20–35 yr) were classified into one of three groups: the active-smoking mothers (n=15), the passive-smoking mothers (n=22), and the nonsmoking mothers (n=23). Serum and milk MDA, SOD, GPx, and AOP values were determined in mothers on the postpartum seventh day by the spectrophotometric method. Serum Zn and Cu concentrations were determined by atomic absorption spectrophotometry (AAS). There was no significant difference in serum samples with respect to MDA (p=0.17), SOD (p=0.51) and AOP (p=0.36) levels, but there was a significant difference in serum GPx (p=0.002) levels among the study groups. The significant differences were also found in milk samples in terms of MDA (p=0.002) and SOD (p=0.011), but not in GPx (p=0.11) and AOP (p=0.29) levels among the study groups. No significant difference was seen in serum zinc concentration (p=0.49), but copper concentration differed significantly among the groups (p=0.005). These observations suggest that human milk is more vulnerable to oxidative stress and lipid peroxidation than serum samples in smoking mothers, even if they are passive smokers.     

Correlation Between Iodine Intake and Thyroid Function in Subjects with Normal Thyroid Function

Excessive iodine intake is known to induce hypothyroidism in people who have underlying thyroid disorders. However, few studies have been performed on subjects with normal thyroid function without a history of autoimmune thyroid disease. We hypothesized that high iodine intake may cause a subtle change in thyroid function even in subjects with normal thyroid function. We analyzed 337 subjects (64 men and 273 women; mean age, 49 years) who showed normal levels of thyroid peroxidase antibodies (TPO-Ab) and thyroglobulin antibodies (Tg-Ab) by measuring the urinary iodine excretion, free T4 (FT4), and thyroid-stimulating hormone (TSH). The results showed urinary iodine excretion had negative correlation with FT4 (γ = −0.11, p = 0.043) and showed a positive trend with TSH (γ = 0.10, p = 0.068). We found that 61.7% of subjects had circulating TPO-Ab within normal reference range. In all subjects, TPO-Ab levels were negatively correlated with FT4 (γ = −0.17, p = 0.002) and positively with TSH (γ = 0.13, p = 0.021). In conclusion, high iodine intake can negatively affect thyroid hormone levels in subjects with normal thyroid function. Population-based study will be helpful for further clarification.     

Iodine Deficiency Among Hypothyroid Patients Living in Jeddah

The objective was to determine the prevalence of iodine deficiency among hypothyroid patients and the effect of dietary goitrogens on indices of iodine and thyroid status. This is a case-control study of 106 subjects who were recruited from King Abdulaziz University Hospital, Jeddah. Blood and urine were collected for serum thyroid hormones, thyroid autoantibodies, thyroglobulin (Tg) and urinary iodine concentration (UIC). Dietary iodine and goitrogenic food intake were assessed by questionnaire. Using World Health Organization (WHO) cutoff values for UIC, both controls and cases were iodine deficient (85% and 83%, respectively). Furthermore, dietary iodine was deficient in 23% of controls and 36% of cases. In cases, there was a positive association between UIC levels and serum thyroid stimulating hormone (r = 0.405, p < 0.01) and a negative association with serum fT₄ (r = −0.358, p < 0.01). Serum Tg antibody titers were also positively associated with dietary iodine (r = 0.328, p < 0.05). Patients with elevated serum autoantibodies had lower UIC and dietary iodine than those with normal serum autoantibodies. UIC was associated with dietary goitrogens including turnip (r = 0.280, p < 0.05) and pine (r = 0.289, p < 0.05) among cases. Iodine deficiency is common and the consumption of dietary goitrogens is high among euthyroid and hypothyroid subjects living in Jeddah.     

Autoimmune disease in mothers with the FMR1 premutation is associated with seizures in their children with fragile X syndrome

An increased prevalence of autoimmune diseases in family members of children with autism spectrum disorders (ASD) has been previously reported. ASD is also a common problem co-occurring in children with fragile X syndrome (FXS). Why ASD occurs in some individuals with FXS, but not all, is largely unknown. Furthermore, in premutation carrier mothers, there is an increased risk for autoimmune diseases. This study compared the rate of ASD and other neurodevelopmental/behavioral problems in 61 children with FXS born to 41 carrier mothers who had autoimmune disease and in 97 children with FXS of 78 carrier mothers who did not have autoimmune disease. There were no significant differences in the mean age (9.61 ± 5.59 vs. 9.41 ± 6.31, P = 0.836), cognitive and adaptive functioning in children of mothers with and without autoimmune disease. Among children whose mothers had autoimmune disease, the odds ratio (OR) for ASD was 1.27 (95% CI 0.62–2.61, P = 0.5115). Interestingly, the OR for seizures and tics was 3.81 (95% CI 1.13–12.86, P = 0.031) and 2.94 (95% CI 1.19–7.24, P = 0.019), respectively, in children of mothers with autoimmune disease compared to children of mothers without autoimmune disease. In conclusion, autoimmune disease in carrier mothers was not associated with the presence of ASD in their children. However, seizures and tics were significantly increased in children of mothers with autoimmune disease. This suggests a potential new mechanism of seizure and tic exacerbation in FXS related to an intergenerational influence from autoimmunity in the carrier mother.     

Advantages of the Use of Deciduous Teeth,Hair, and Blood Analysis for Lead and Cadmium Bio-Monitoring in Children. A Study of 6-Year-Old Children from Krakow (Poland)

The population of about 300 6-year-old preschool children was studied for lead (Pb) and cadmium (Cd) in deciduous teeth, scalp hair, and capillary blood. Zinc (Zn) content in hair was also measured due to its possible interferences with the elements studied. The Pb and Cd contents were measured by graphite furnace atomic absorption spectrometry with Zeeman background correction, and Zn, by flame method. Metal levels found were comparable to those in European countries. Positive correlations between Pb and Cd in the same and different tissues were widespread (r = 0.23–0.68). A positive correlation was found between Pb in teeth and blood (r = 0.65, p < 0.001). Pb blood threshold 100 μg L⁻¹ referred to 2.6 μg g⁻¹ Pb in teeth. Predictability of this Pb teeth limit was 14% vs. 5% for Pb blood. Strong negative correlation was found between hair Pb and Zn (r = −0.68, p < 0.001). Enhanced Cd and Zn levels in hair were associated with the household drinking water hardness. The associations with some other environmental and behavioral factors were also presented and discussed. The results proved the advantage of analysis of primary teeth for Pb exposure screening of preschool children.     

Copper and Zinc in the Serum,Urine, and Hair of Patients with Wilson’s Disease Treated with Penicillamine and Zinc

The purpose of this study was to determine the different levels of copper and zinc in the serum, urine, and scalp hair of patients with Wilson’s disease receiving different, currently accepted methods of treatment to reduce the copper load (penicillamine—group 1, n = 8; zinc—group 2, n = 8; penicillamine+zinc—group 3, n = 8). Blood, urine, and hair samples were collected from the patients. All three treatments resulted in a significant decrease of the serum copper levels. Significantly increased levels of zinc in the serum were detected in the patients in groups 2 and 3 (19.1 and 18.8 μmol/l, respectively; p < 0.05). Copper excretion in the urine significantly increased during its administration to groups 1 and 3 (11.5 and 7.94 μmol/24 h respectively; p < 0.001) due to the effect of penicillamine. The administration of zinc as monotherapy (group 2) or in combination with penicillamine (group 3) led to an increase of its excretion (25.3 and 22.4 μmol/24 h, respectively; p < 0.01). Only an insignificant rise of the copper content in the hair was found in all three groups of patients. The content of zinc in the hair did not differ significantly in any of the groups in comparison with the control group.     

Some essential elements in maternal and cord blood in relation to birth weight and gestational age of the baby

Maternal and cord blood were collected from 54 Indian women at parturition and analyzed for Zn, Cu, and Fe by flame atomic absorption spectrophotometry to determine the relationship between levels of these elements in mother’s and infant’s blood and maternal age, birth weight, and gestational age of the baby. The blood Zn level of mothers in the age group 24–28 yr was significantly higher than those of mothers in the age group of 18–23 yr (p<0.05). Similarly, mothers in the 24 to 28-yr group also had higher blood Fe level than mothers in the group 29–38 yr (p<0.05). The levels of Zn, Cu, and Fe were higher in the maternal blood and lower, but not significantly, in the cord blood of low-birth-weight babies than in those of normal-birth-weight babies. However, differences in the levels of Zn, Cu, and Fe between maternal and cord blood of the two birth-weight groups was statistically significant. There were no significant differences in the levels of the three elements in maternal or cord blood by the gestational age of the baby. A weak but significant correlation was found between the birth weight of the baby and the Fe level in the cord blood (r=0.26; p<0.05). Also, weak significant correlations were observed between gestational age of the baby and Fe (r=0.23; p<0.05) and Cu (r=0.31; p<0.05) levels in the cord blood. Although, there are many confounders of low birth weight and preterm deliveries, a diminished placental transfer of these essential elements could be one of the several etiological factors for low birth weight of newborns.     

Iodine intakes assessed by urinary iodine concentrations in healthy children aged ten months,two years,and four years

Urinary iodine excretion was assessed in 642 healthy children aged 10 mo (n=243), 2 yr (n=183), and 4 yr (n=216) living in the Paris area and originating from continental France (60.3%), North Africa (13.8%), the West Indies (9.1%), West Africa (8.3%), Southeast Asia (4.8%), and southern Europe (3.8%). Mild impairment of neurological (reflexes, tone, audiometry) and intellectual development (Brunet-Lézine scale) was assessed in relation to iodine status. Iodine excretions (median values) were 18.4, 11.9, and 10.9 μg/100 mL at 10 mo, 2 yr, and 4 yr, respectively, and risk of mild iodine deficiency (5–10 μg/100 mL) was 18.1%, 34.8%, and 38.3% for the same age groups. No relationship was found between anthropometry, global development quotient, and iodine status. High hearing thresholds were more commonly associated with lower iodine excretion, suggesting mild hearing defects. In spite of iodine prophylaxis, the risk of mild to moderate iodine deficiency still exists in France and in a number of European countries. Evaluation of neurological sequels of borderline iodine status is a major public health problem in European communities.     

Trace Elements Analysis of Urine and Hair in Tuberculous Pleurisy

In this study, copper, zinc, magnesium, manganese, selenium, and iron of urine and hair were measured in the patients with tuberculous (TB) pleurisy (n = 24) and in the control group (n = 20). Selenium, magnesium, and zinc of hair were found to be significantly lower in TB pleurisy cases than those in the control group (p < 0.05, p < 0.001, and p < 0.01, respectively). On the contrary, selenium and magnesium of urine were found to be significantly elevated in TB pleurisy cases than those in the control group (p < 0.05 and p < 0.001, respectively). There was no significant difference in the value of manganese and iron between TB pleurisy and the control group (p > 0.05). Copper level were significantly increased in hair and decreased in urine of the patients (p < 0.01). The occurrence of these abnormalities constitutes new information regarding trace elements in TB pleurisy patients. These results may provide an additional disease correlate for assessing TB pleurisy risk.     

Lead,copper, zinc,and magnesium levels in hair of children and young people with some disorders of the osteomuscular articular system

The lead, copper, zinc, and magnesium contents of scalp hair taken from 173 children aged 1–15 yr and young people (16–18 yr) with certain disorders of the osteomuscular articular system (osteomuscular pains of unknown origin, once described as “growing pains”) were measured, using the flame atomic absorption spectrometry method, and then compared with those of 108 normal, healthy children. The research showed increased average levels of lead (a statistically significant p<0.05 in both the overall group of children, and in those over 11 yr old), and zinc (increased in the total group, in a statistically significant way at p<0.10 only in adolescents over 15 yr old) and decreased levels of copper (although not significantly) in the hair of children suffering from “rheumatic” diseases, as compared with controls. The magnesium levels for the total group of ill children were admittedly enhanced, but in the youngest children, the levels were reduced. The values of the Mg/Pb and Mg/Zn ratios were lower (in the youngest children, 70% decrease of the Mg/Pb ratio) and Zn/Cu were higher in the group of children suffering from rheumatic diseases than in the healthy children. The difference of Mg/Pb ratio between the total controls and rheumatic subjects was statistically significant at p<0.05 and the Zn/Cu at p<0.10. The Mg/Zn ratio was not statistically significant.     

Assessment of Trace Elements in Scalp Hair of a Young Urban Population in Brazil

The aim of this study was to establish background values for toxic and essential elements in hair, interelement correlations and the differences in levels between genders in a healthy young population from Southern Brazil. Hair samples (n = 167) were collected from healthy students aged 12–18 years. Trace element concentrations in hair were determined by inductively coupled plasma mass spectrometry. The study provided relatively low values for toxic elements and balanced concentrations for the essential elements in the adolescents' hair with reliable reference data. Interestingly, this study also demonstrated statistical correlations considered newfound between the elements in hair. Hair mercury levels were influenced by gender; with males presenting higher values. The overall findings of the present study, with respect to the estimated chemical elements, are of prime importance in the evaluation of reference values for determining environmental effects on children living in urban areas.     

Selenium concentration in blood and hair of holstein dairy cows

Four-hundred Holstein cows in 40 dairy farms in north Greece were included in this study, and blood (n=400), black hair (n=400), white hair (n=40), and feed (n=40) samples were obtained. Although the feeding regime in these farms was similar, the selenium content of feeds was variable. The Se content of concentrate feeds was 0.104±0.086 mg/kg dry matter (DM), and of silage, it was 0.025±0.018 mg/kg. A significantly positive correlation was found between the Se concentration in black hair and the Se concentration in blood (r ²=0.610, p<0.001), the Se concentration in white hair and the Se concentration in blood (r ²=0.770, p<0.001), and the Se concentration in white hair and the Se concentration in black hair (r ²=0.921, p<0.001). The Se concentration in white hair was significantly smaller than that in black hair (p<0.001).     

Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodeficiency virus-1 infection

Serum selenium levels were determined cross-sectionally in 57 HIV-infected patients who were classified according to the Centers for Disease Control (CDC) 1993 classification system. Mean serum selenium levels were lower in CDC stage II (58.7±12.2 μg/L;p<0.01;n=18) and stage III (47.6±11.3 μg/L;p<0.01;n=19) HIV-infected patients, than in healthy subjects (80.6±9.6 μg/L;n=48) and stage I patients (73.6±16.5 μg/L;n=20). Serum selenium levels were positively correlated with CD4 count, CD4/8 ratio, hematocrit, and serum albumin (r=0.42;r=0.39;r=0.48; andr=0.45;p<0.01, respectively) and inversely with serum levels of thymidine kinase (r=−0.49;p<0.01;n=49) and β2-microglobulin (r=−0.46;p<0.001;n=49). In addition, serum selenium levels in 20 randomly selected AIDS-free individuals (CDC I:n=10; CDC II:n=10) were inversely correlated with serum concentrations of interleukin-8 (IL-8) and soluble tumor necrosis factor receptors (sTNFR) types I and II. There was no correlation with serum immuneglobulin A and total serum protein levels. The results show that the progressive deprivation of serum selenium in HIV-infection is associated with loss of CD4⁺-cells and with increased levels of markers of disease progression and inflammatory response.     

Serum and hair levels of zinc, selenium, iron, and copper in children with iron-deficiency anemia

In the present study, the serum and hair levels of zinc, selenium, and copper were determined in children with iron-deficiency anemia (IDA). A total of 52 anemic children aged 1–4 yr constituted the study group. Fortysix healthy children acted as controls. The copper and zinc levels were measured with an atomic absorption spectrophometer. Serum and hair selenium was determined by a spectroflourometric method. The serum zinc and selenium concentrations in the IDA group were found to be significantly lower and serum copper significantly higher than those in the controls (p<0.05). Lower iron, zinc, and selenium concentrations (p<0.001) but not copper were found in hair (p>0.05).     

Relationship Between Serum Calcium and Magnesium Concentrations and Metabolic Syndrome Diagnostic Components in Middle-Aged Korean Men

It is thought that calcium and magnesium may be related to metabolic disorders such as obesity and metabolic syndrome; however, to date, there have been few studies investigating the association between serum calcium and magnesium levels and metabolic syndrome in middle-aged male adults. We aimed to investigate the association between serum calcium and magnesium levels and metabolic syndrome in Korean middle-aged male adults. Study subjects included 213 men aged 30∼60 years. MetS risk score is determined by adding the number of risk factors, waist circumference, triacylglyceride (TG), HDL cholesterol, glucose, and blood pressure (BP). The study population was divided into three groups according to the MetS risk score: group I (MetS risk score ≤1; n = 106), group II (MetS risk score = 2; n = 51), and group III (MetS risk score ≥3; n = 56). The serum Ca, according to increase of MetS risk score, was significantly higher (p < 0.001), and there was no significant difference in serum Mg concentration among the three groups. Subjects with high TG and high BP had higher serum calcium levels than those without such abnormalities. Subjects with higher glucose had lower serum magnesium levels than those without such abnormality. The correlation analysis indicated that the serum Ca had positive correlations with the MetS risk score (r = 0.1769, p < 0.01), serum TG (r = 0.2516, p < 0.001), and DBP (r = 0.2246, p < 0.01). The correlation analysis indicated that the serum Mg had an inverse relationship with serum glucose (r = −0.2404, p < 0.001). In conclusion, serum Ca had positive association with TG and BP, while serum Mg had negative association with serum glucose after adjusting age and BMI among the middle-aged Korean male adults.     

Relative and combined effects of ethanol and protein deficiency on some hair trace elements

This study was performed in order to analyze the relative and combined effects of ethanol and protein deficiency on hair copper, zinc, manganese, and iron content in four groups of seven animals each which were pair-fed during 8 wk with (1) a nutritionally adequate diet, (2) a 36% (as energy) ethanol-containing isocaloric diet, (3) a 2% protein, isocaloric diet, and (4) a 36% ethanol, 2% protein isocaloric diet, respectively, following the Lieber-DeCarli model, and to analyze the relationship between hair copper, zinc, manganese, and iron content, and the liver and muscle content of these elements. Although there was a trend to higher levels of all the elements analyzed in the the hair of the low-protein fed animals, differences were statistically significant regarding copper and manganese, effects being solely attributable to the low protein diet, not to ethanol. Moreover, hair copper was significantly, inversely related with final weight and weight loss. There were significant relationship between liver zinc and muscle zinc (r=0.57, p=0.002), but not between liver or muscle zinc and hair zinc; no correlations were observed between muscle copper and hair copper, nor between liver manganese and hair manganese. An inverse, statistically significant correlation was observed between liver copper and hair copper (r=−0.39, p<0.05).     

Polymorphism in intron 1 of the interferon-gamma gene influences both serum immunoglobulin E levels and the risk for chronic hepatitis B virus infection in Polynesians

Intron 1 of the interferon-gamma (IFNG) gene contains two polymorphisms. The 12 CA-repeat allele of the +875 IFNGCA microsatellite and the T allele of the +A874T single nucleotide polymorphism (SNP) have been associated with increased in vitro IFNG production and a variety of clinical phenotypes. The purpose of this study was to determine whether these polymorphisms influence total serum IgE levels [tsIgE] and the outcome of a hepatitis B virus (HBV) infection. IFNGCA and +A874T were typed in 186 asthmatics of Niuean ancestry and in Polynesian women with a chronic HBV infection (n = 60) and with natural immunity to the HBV (n = 66). The IFNGCA genotype was associated with [tsIgE] in asthmatic children (n = 51, p = 0.004) but not adults (n = 135, p = 0.87). The data were consistent with a co-dominant influence of the 12 CA-repeat allele on high [tsIgE]. The IFNGCA genotype was also associated with the risk for chronic HBV infection (χ ² = 11.6, p = 0.003) because of a dominant effect of the 12 CA-repeat allele on developing natural immunity in homozygotes (OR = 5.8, p = 0.003) and heterozygotes (OR = 2.7, p = 0.01). Similar associations were found for the T allele of the +A874T SNP. The possibility that these associations were due to linked alleles in the adjacent 783 bp of the promoter and 3′-untranslated region of the IFNG gene was excluded by direct sequencing. In summary, high-IFNG-producing alleles in intron 1 of the IFNG locus are associated with high [tsIgE] in asthmatic children from Niue and with natural immunity to the HBV in Polynesian women. These findings are consistent with a previous report of an association between +875 IFNGCA and [tsIgE] and provide preliminary evidence of a new association with the outcome of an HBV infection.