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BACKGROUND: Questionnaire-based studies investigating blood donation history rely on the accurate recall of information from participants for results to be valid. This study aimed to retrieve electronic records from a national blood donation service and link them to self-reported history of donation to assess agreement between the two sources. STUDY DESIGN AND METHODS: Between 2004 and 2006, a sample of participants of northern European descent was selected from the Melbourne Collaborative Cohort Study (n = 31,192) to participate in the 'HealthIron' study (n = 1438). A total of 1052 participants completed questionnaires that included questions about blood donation history. In 2009, consenting participants' records were linked to the Australian Red Cross Blood Service (ARCBS) to provide information on blood donations made between 1980 and follow-up (2004-2006). Those who commenced blood donation before 1980 were excluded. RESULTS: A total of 718 participants were available for analysis. Of these, 394 (55%) provided signed consent, including 182 (82%) of the 227 participants who self-reported ever donating blood. The two data sources were concordant for 331 (87%) of participants, with a κ statistic of 0.74 (SE, 0.05) indicating a high level of agreement. Participants tended to overstate by a factor of 2.0 (95% confidence interval, 1.7-2.2) the number of donations they had made when compared with ARCBS records. CONCLUSION: Participants in studies assessing self-reported blood donation history are likely to correctly indicate whether or not they have ever donated blood. Quantitative estimates are potentially inaccurate and could benefit from validating a sample of records to quantify the bias. [ABSTRACT FROM AUTHOR]

Homozygosity for the p.C282Y substitution in the HFE protein encoded by the hemochromatosis gene on chromosome 6p (HFE) is a common genetic trait that increases susceptibility to iron overload. McLaren et al. used bivariate mixture modeling to analyze the joint population distribution of transferrin saturation (TS) and serum ferritin concentration (SF) measured for participants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. They identified four components (C1, C2, C3, and C4) with successively increasing means for TS and SF. They demonstrated that bivariate mixture modeling in TS and SF reflect the genetic locus of HFE and may isolate p.C282Y homozygotes from the general population. In the current study we used data from the another large cohort, the Australian HealthIron study of genetic and environmental modifiers of hereditary hemochromatosis, to validate the component analysis approach, to examine stability of component proportions over time and to determine if TS and SF values from an individual move between components at baseline and follow-up. Because sampling fractions from each p.C282Y / p.H63D genotype stratum are not equal, we used frequency weights based on the inverse of the probability of selection for invitation to participate. In the weighted female analytic cohorts, C4 captured most of C282Y homozygotes, and C2 was the largest component. We identified four components from the weighted male analytic cohort and C4 captured most of p.C282Y homozygotes. The bivariate mixture modeling approach suggested that the model is transferable from one white population to another, although estimated means within components may differ. [ABSTRACT FROM AUTHOR]

Background and Aim Women who are homozygous for the p.C282Y mutation in the HFE gene are at much lower risk of iron overload-related disease than p.C282Y homozygous men, presumably because of the iron-depleting effects of menstruation and pregnancy. We used data from a population cohort study to model the impact of menstruation cessation at menopause on serum ferritin (SF) levels in female p.C282Y homozygotes, with p.C282Y/p.H63D simple or compound heterozygotes and those with neither p.C282Y nor p.H63D mutations ( HFE wild types) as comparison groups. Methods A sample of the Melbourne Collaborative Cohort Study was selected for the 'HealthIron' study ( n = 1438) including all HFE p.C282Y homozygotes plus a random sample stratified by HFE-genotype (p.C282Y and p.H63D). The relationship between the natural logarithm of SF and time since menopause was examined using linear mixed models incorporating spline smoothing. Results For p.C282Y homozygotes, SF increased by a factor of 3.6 (95% CI (1.8, 7.0), P < 0.001) during the first 10 years postmenopause, after which SF continued to increase but at less than half the previous rate. In contrast, SF profiles for other HFE genotype groups increase more gradually and did not show a distinction between premenopausal and postmenopausal SF levels. Only p.C282Y homozygotes had predicted SF exceeding 200 μg/L postmenopause, but the projected SF did not increase the risk of iron overload-related disease. Conclusions These data provide the first documented evidence that physiological blood loss is a major factor in determining the marked gender difference in expression of p.C282Y homozygosity. [ABSTRACT FROM AUTHOR]

Background and Aim The risk of hemochromatosis-related morbidity for HFE simple heterozygosity for either the C282 Y or H63 D substitutions in the HFE protein was assessed using a prospective community-based cohort study. Methods HFE genotypes were measured for 31 192 persons of northern European descent, aged between 40 and 69 years when recruited to the Melbourne Collaborative Cohort Study, and subjects were followed for an average of 12 years. For a random sample of 1438 participants stratified according to HFE genotype, two sets of biochemical iron indices performed 12 years apart and, at follow-up only, the presence/absence of six disease features associated with hereditary hemochromatosis were obtained. Summary data for 257 (139 female) C282 Y simple heterozygotes and 123 (74 female) H63 D simple heterozygotes were compared with 330 (181 female) controls with neither HFE mutation. Results At baseline, mean transferrin saturation ( TS) (95% confidence interval) and prevalence of TS > 55% were 35.14% (33.25, 37.04) and 3/112 (3%), 33.03% (29.9, 36.15) and 0/39 (0%), and 29.67% (27.93, 31.4) and 3/135 (2%) for C282 Y, H63 D and wild-type male participants, respectively. At follow-up, mean TS levels remained similar to baseline levels for both men and women irrespective of simple heterozygosity for either mutation. No HFE C282 Y or H63 D simple heterozygotes had documented iron overload (based on hepatic iron measures or serum ferritin greater than 1000 mg/ L at baseline with documented therapeutic venesection). Conclusion No documented iron overload was observed for HFE simple heterozygotes for either C282 Y or H63 D, and morbidity for both HFE simple heterozygote groups was similar to that of HFE wild-type participants. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To examine concordance between two self-reported measures of puberty: Sexual Maturation Scale (SMS) and Pubertal Development Scale (PDS) and their acceptability to adolescents. Methods: Participants of a school-based study in grades 5, 7 and 9 were classified into one of 5 pubertal stages using each method. Results: 2864 students (age 9–16 years) participated. Agreement was moderate for males ( 0.42, 95% CI 0.39, 0.45) and females ( 0.57, 95% CI 0.53, 0.61). Concordance within one stage was excellent (females 97%, males 89%), with discrepancies due to females being classified one stage later on the PDS (26%) and males one stage earlier (32%). There were more missing data for the SMS (13%) than the PDS (4%). Conclusions: Given the level of concordance and difficulties of using the drawings in a school-based survey, we would recommend the PDS as an alternative to assess pubertal status in epidemiological studies. [Copyright &y& Elsevier]

There is emerging evidence that there are genetic modifiers of iron indices for HFE gene mutation carriers at risk of hereditary hemochromatosis. A random sample, stratified by HFE genotype, of 863 from a cohort of 31 192 people of northern European descent provided blood samples for genotyping of 476 single nucleotide polymorphisms (SNPs) in 44 genes involved in iron metabolism. Single SNP association testing, using linear regression models adjusted for sex, menopause and HFE genotype, was conducted for four continuously distributed outcomes: serum ferritin (log transformed), transferrin saturation, serum transferrin, and serum iron. The SNP rs884409 in CYBRD1 is a novel modifier specific to HFE C282Y homozygotes. Median unadjusted serum ferritin concentration decreased from 1194 μg/l ( N = 27) to 387 μg/l ( N = 16) for male C282Y homozygotes and from 357 μg/l ( N = 42) to 69 μg/l ( N = 12) for females, comparing those with no copies to those with one copy of rs884409. Functional testing of this CYBRD1 promoter polymorphism using a heterologous expression assay resulted in a 30% decrease in basal promoter activity relative to the common genotype ( P = 0·004). This putative genetic modifier of iron overload expression accounts for 11% (95% CI 0·4%, 22·6%) of the variance in serum ferritin levels of C282Y homozygotes. [ABSTRACT FROM AUTHOR]