Lise Wegner Thørner

Predictors of iron levels in 14,737 Danish blood donors: results from the Danish Blood Donor Study

Dietary studies show a relationship between the intake of iron enhancers and inhibitors and iron stores in the general population. However, the impact of dietary factors on the iron stores of blood donors, whose iron status is affected by blood donations, is incompletely understood.

Promoter variants in IL18 are associated with onset of depression in patients previously exposed to stressful-life events.

BACKGROUND Depression is accompanied by an inflammatory reaction and activation of cell mediated immunity (CMI) and stressors may induce the cytokine network in humans. The proinflammatory cytokine interleukin-18 (IL-18) is less investigated in depression but highly relevant since it is produced by activated macrophages and expressed in the brain. METHODS The distribution of six polymorphisms in IL10, IL18 and NF was compared between patients with a single episode of depression either preceded by a stressful life event (n=182), or occurring without a prior stressful life event (n=106) and a group of healthy control individuals (n=335). RESULTS The major C allele of the IL18 rs187238 and the major G allele of rs1946518 had a significantly higher prevalence among the patients with a stressful life event prior to onset of disease than both patients without a stressful life event and compared with the healthy controls individuals. None of the examined IL10 or NF alleles were differently distributed among these groups. LIMITATIONS Data are nominally significant and not resistant to correction for multiple testing. CONCLUSION The major C allele of the IL18 rs187238 and the major G allele rs1946518 have previously been associated with higher expression of IL-18 mRNA. Our data suggest that this genetic trend towards higher IL-18 production may increase the susceptibility to depression in response to stressful life events.

Combined Oral Contraception and Obesity Are Strong Predictors of Low-Grade Inflammation in Healthy Individuals: Results from the Danish Blood Donor Study (DBDS)

Background C-reactive protein (CRP) is a well-established marker of inflammation. The level of CRP is affected by several lifestyle factors. A slightly increased CRP level, also known as low-grade inflammation (LGI), is associated with increased risk of several diseases, especially cardiovascular disease. The aim of this study was to identify predictors of increased CRP levels in healthy individuals. We therefore assessed CRP in a large cohort of blood donors. Methods We measured plasma CRP levels in 15,684 participants from the Danish Blood Donor Study. CRP was measured by a commercial assay. Furthermore, all participants completed a standard questionnaire on smoking status, alcohol consumption, physical activity, diet, and various body measurements. Female participants also reported the use of contraception, childbirth, and menopausal status. The relationship between LGI (defined here as a plasma CRP level between 3 mg/L and 10 mg/L) and predictors was explored by multivariable logistic regression analysis. Results were presented as odds ratios (OR) with 95% confidence intervals (CI). Results We found LGI in a total of 1,561 (10.0%) participants. LGI was more frequent in women using combined oral contraception (OC) (29.9%) than in men (6.1%) and women not using OC (7.9%). Among premenopausal women, OC was the strongest predictor of LGI (odds ratio = 8.98, p<0.001). Additionally, body mass index (BMI) and waist circumference were positively associated with LGI. Conclusion High BMI and abdominal obesity strongly predicted LGI among healthy individuals. However, the most striking finding was the high prevalence of LGI among premenopausal women who used combined oral contraception. Although the significance of CRP as a marker of inflammation is well known, the role of CRP in pathogenesis is still uncertain. The impact of oral contraception on CRP levels should nevertheless be considered when CRP is used in risk assessment.

Obesity and risk of infection: results from the Danish Blood Donor Study.

Background: It is well known that obesity complicates the course of several diseases. However, it is unknown whether obesity affects the risk of infection among healthy individuals. Methods: We included 37,808 healthy participants from the Danish Blood Donor Study, who completed a questionnaire on health-related items. Obesity was defined as a body mass index ≥ 30 kg/m2. Infections among participants were identified by relevant ICD-10 codes in the Danish National Patient Register and Anatomical Therapeutic Chemical (ATC) codes in the Danish Prescription Register. Multivariable Cox proportional hazards analysis with age as the underlying timescale was used as the statistical model. Results: During 113,717 person-years of observation, 1,233 participants were treated for infection at a hospital. Similarly, during 58,411 person-years of observation, 15,856 participants filled at least one prescription of antimicrobials. Obesity was associated with risk of hospital-based treatment for infection (women: hazard ratio [HR] = 1.5, 95% confidence interval [CI] = 1.1, 1.9; men: HR = 1.5, 95% CI = 1.2, 1.9). For specific infections, obesity was associated with increased risk of abscesses (both sexes), infections of the skin and subcutaneous tissue (men), and respiratory tract infections and cystitis (women). Similarly, obesity was associated with filled prescriptions of antimicrobials overall (women: HR = 1.22, 95% CI = 1.14, 1.30; men: HR = 1.23, 95% CI: 1.15, 1.33) and particularly with phenoxymethylpenicillin, macrolides, dicloxacillin and flucloxacillin, and broad-spectrum penicillins. Conclusions: In a large cohort of healthy individuals, obesity was associated with risk of infection. This result warrants further studies of metabolism and the immune response.

No association between iron status and self-reported health-related quality of life in 16,375 Danish blood donors: results from the Danish Blood Donor Study.

Health‐related quality of life (HRQL) represents peoples subjective assessment of their mental and physical well‐being. HRQL is highly predictive of future health. The effect of iron deficiency without anemia induced by blood donation on HRQL is presently unknown. The aim was to explore the relationship between iron status and self‐reported mental component score (MCS; SF‐12) and physical component score (PCS; SF‐12) in Danish blood donors.

Polymorphism in interleukin-7 receptor α gene is associated with faster CD4⁺ T-cell recovery after initiation of combination antiretroviral therapy

Objectives:To investigate single-nucleotide polymorphisms (SNPs) in the gene encoding interleukin-7 receptor &agr; (IL7RA) as predictors for CD4+ T-cell change after initiation of combination antiretroviral therapy (cART) in HIV-infected whites. Design:SNPs in IL7RA were determined in the Danish HIV Cohort Study. Methods:CD4+ T-cell changes were estimated 6 months, 1, 2, and 5 years after initiation of cART in 1683 HIV-infected virally suppressed individuals. Five SNPs in IL7RA were examined as predictors for CD4+ T-cell change in the first (0–6 months after initiation of cART) and second phase (>6 months after initiation of cART) of immune recovery. Univariable and multivariable analyses including age, sex, calendar period, CD4+ nadir, and baseline CD4+ T-cell count and viral load as covariates were performed. Results:Individuals carrying two T-alleles in rs6897932 had faster CD4+ T-cell recovery compared with individuals carrying a C-allele in the first phase of immune recovery [mean CD4+ T-cell change, cells/&mgr;L (95% confidence interval), in TT: 177 (151–203), CT: 131 (119–143), CC: 141 (132–151), P = 0.018]. No isolated effect of rs6897932 on CD4+ T-cell change was found in the second phase of immune recovery; however, the initial difference in CD4+ T-cell recovery remained during 5 years. The effect was most pronounced in individuals above 40 years of age. Conclusion:T-allele homozygosity in rs6897932 is a predictor for faster CD4+ T-cell recovery after initiation of cART in HIV-infected whites, however, only in the first phase of immune recovery.

HLA-G 3′ Untranslated Region 14–Base Pair Deletion: Association With Poor Survival in an HIV-1–Infected Zimbabwean Population

We aimed to evaluate whether the HLA-G 14-base pair (bp) polymorphism (rs16375) has an impact on human immunodeficiency virus HIV progression and survival in an antiretroviral therapy-naive Zimbabwean cohort (n = 312). Rs16375 was genotyped using a competitive allele-specific polymerase chain reaction system; CD4 cell counts and HIV RNA were measured with flow cytometry and commercially available polymerase chain reaction; survival was followed up for 4.3 years. The homozygous HLA-G -14-bp genotype is associated with higher viral load (P = .004), lower CD4 cell count (P = .01), and increased mortality (hazard ratio, 1.9; 95% confidence interval, 1.033-3.522; P = .04) compared with HLA-G +14-bp carriers.

Predictors of hemoglobin in Danish blood donors: results from the Danish Blood Donor Study.

It is well known that blood donors are at increased risk of iron deficiency and subsequent development of iron deficiency anemia. We aimed to investigate the effect of factors influencing hemoglobin (Hb) levels.

CCL3L gene copy number and survival in an HIV-1 infected Zimbabwean population

The C-C motif chemokine ligand 3-like (CCL3L) protein is a potent chemoattractant which by binding to C-C chemokine receptor type 5 (CCR5) inhibits human immunodeficiency virus (HIV) entry. Copy number variation (CNV) of the CCL3L has been shown to be associated with HIV susceptibility and progression to AIDS, but these results have been inconsistent. We examined a Zimbabwean study population for an association of CCL3L CNV with HIV status, progression (CD4 T-cells and viral load), and survival. Another aim was to investigate the possible effects of CCL3L CNV on CCL3 protein concentration. A treatment-naïve cohort, which included 153 HIV infected and 159 HIV uninfected individuals, was followed for up to 4.3 years. The CNV of the CCL3L was determined by duplex real-time polymerase chain reaction. We found no association between four CCL3L CNV strata and HIV status (P=0.7), CD4 T-cell count (P=0.9), viral load (P=0.9), or CCL3 protein levels (P=1.0). Survival among the HIV infected individuals did not differ according to CCL3L copy number. In this cohort, CCL3L CNV did not affect HIV status, pathogenesis, or survival.

The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement

Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We used six independent case–control studies from five different countries (Sweden, Denmark, Norway, Serbia, United States). A pooled analysis was performed for replication of previous observations (7190 cases, 8876 controls). Refined detailed analyses were carried out by combining the genetically similar populations from the Nordic studies (6265 cases, 8401 controls). In both the pooled analyses and in the combined Nordic material, interactions were observed between HLA-DRB*15 and absence of HLA-A*02 and between smoking and each of the genetic risk factors. Two way interactions were observed between each combination of the three variables, invariant over categories of the third. Further, there was also a three way interaction between the risk factors. The difference in MS risk between the extremes was considerable; smokers carrying HLA-DRB1*15 and lacking HLA-A*02 had a 13-fold increased risk compared with never smokers without these genetic risk factors (OR 12.7, 95% CI 10.8–14.9). The risk of MS associated with HLA genotypes is strongly influenced by smoking status and vice versa. Since the function of HLA molecules is to present peptide antigens to T cells, the demonstrated interactions strongly suggest that smoking alters MS risk through actions on adaptive immunity.