The role of estrogen receptor-α gene TA polymorphism and aromatase gene TTTA polymorphism on peak bone mass attainment in males: is there an additive negative effect of certain allele combinations?

Idiopathic osteoporosis in males is influenced predominantly by low peak bone mass as a feature under a strong genetic control. Among a number of candidate genes, α-estrogen receptor (ERα) and CYP19 genes are of particular interest due to important role of estrogen in pathophysiology of osteoporosis. In the present study we examined the association of certain allelic combinations of ERα gene thymine–adenine (TA) polymorphism and aromatase gene TTTA polymorphism on bone mineral density (BMD) in young men. The study sample consisted of 92 unrelated healthy male volunteers, aged 21–35. In each subject, lumbar spine and proximal femur BMD, parameters of bone turnover and 25-OHD level were measured. Two ERα (TA) _n alleles, allele 19 and allele 21, were found to be associated with lower BMD. The presence of allele 19 was associated with significantly lower lumbar spine (P = 0.006) and trochanter (P = 0.02) BMD while the subjects positive for allele 21 had significantly lower lumbar spine (P = 0.04), trochanter (P = 0.02) and total hip (P = 0.03) BMD. Men with CYP19 (TTTA)_7-3/ERα (TA)₁₉ allele combination had significantly lower lumbar spine BMD (P = 0.02) and those with CYP19 (TTTA)_7-3/ERα (TA)₂₁ allele combination had significantly lower BMD for all three measurements, i.e. lumbar spine (P = 0.02), femoral neck (P = 0.02) and total hip (P = 0.008). These particular combinations of high-risk alleles were associated with lower median lumbar spine, femoral neck and total hip BMD than either of the allele alone suggesting that negative effect of two risk alleles on peak bone mass add up.     

Ambient particle source apportionment and daily hospital admissions among children and elderly in Copenhagen

An association between particulate air pollution and morbidity and mortality is well established. However, little is known about which sources of particulate matter contribute most to the adverse health effects. Identification of responsible sources would merit more efficient control. For a 6-year period (01 January 1999 to 31 December 2004), we examined associations between urban background PM(10) in the presence of gaseous pollutants (CO, NO(2)) and hospital admissions due to cardiovascular and respiratory disease in the elderly (age>/=65), and asthma in children (age 5-18) in Copenhagen, Denmark. We further studied associations between fractions of PM(10) assigned to six sources (biomass, secondary, oil, crustal, sea salt, and vehicle) and admissions during a 1(1/2) -year campaign. We used Poisson generalized additive time-series model adjusted for season, day of the week, public holidays, influenza epidemics, grass pollen, school holidays, and meteorology, with up to 5 days lagged air pollution exposure. We found positive associations between PM(10) and the three health outcomes, with strongest associations for asthma. The PM(10) effect remained robust in the presence of CO and NO(2). We found different PM(10) sources to be variably associated with different outcomes: crustal and secondary sources showed strongest associations with cardiovascular, biomass with respiratory, and vehicle with asthma admissions. These novel results may merit future research of potential mechanism, whereas at present, no single PM(10) source can be attributed to all morbidity.     

Lithium influences whole‐organism metabolic rate in Drosophila subobscura

Lithium is widely used to treat bipolar disorder. However, the efficacy and vulnerability as to its side effects are known to differ. Although the specific biochemical mechanism of action is still elusive, lithium may influence mitochondrial function, and consequently, metabolism. Lithium exposure in this study was conducted on a unique set of mito‐nuclear introgression lines of Drosophila subobscura to disentangle the independent effects of mitochondrial DNA (mtDNA) against a common nuclear DNA background. The study addressed three issues: (a) whether lithium has a dose‐dependent effect on whole‐organism metabolic rate, (b) whether mtDNA haplotypes show divergent metabolic efficiency measured by metabolic rate to lithium exposure and (c) whether lithium influences the whole‐organism metabolic rate across sexes. The results confirm that lithium influenced the whole‐organism metabolic rate, showing a subtle balance between efficacy and adverse effects within a narrow dose range. In addition, lithium exposure was found to influence metabolism differently based on mtDNA haplotypes and sex. This preliminary research may have a range of biological implications for the role of mitochondrial variability in psychiatric disease and treatment by contributing to the understanding and predicting of the lithium treatment response and risk for toxic side effects.     

Assessing donor suitability for blood donation: Utility of Geenius HIV 1/2 confirmatory assay

BackgroundBlood donor care and blood safety require a quick and accurate decision on the presence or absence of Human Immunodeficiency Virus (HIV) infection, based on the proper selection of blood donors, serological and molecular HIV testing as well as western blot test. The aim was investigating the possibility of inclusion of Geenius HIV 1/2 Confirmatory Assay in blood donor testing algorithm in order to shorten test time and decrease the number of indeterminate results.MethodsA total of 75 archived serum/plasma samples were tested. Their previous serological and molecular HIV results were: 3 negative samples, 7 positive samples, 65 serological indeterminate or positive but confirmatory testing and NAT negative samples.ResultsGeenius assay confirmed the presence of antibodies in all blood donors with HIV positive serology and Nucleic Acid Testing (NAT). HIV-1 gp160 and gp41 antibodies were detected in these donors, while p31 and p24 antibodies were not detected in two and three donors, respectively. HIV-2 antibodies gp36 and gp140 were not found. Blood donor with HIV indeterminate or positive serology but negative confirmatory testing and NAT, were negative in Geenius assay.Conclusion The results obtained are consistent with western blot results. The assay proved simple and quick to perform. Studies have confirmed the possibility of introducing Bio-Rad Geenius into a routine blood donor testing protocol.     

Childhood tuberculosis: an ancient disease in the youngest generation in the 21st century from epidemiological point of view

Childhood tuberculosis (TB) has distinct epidemiological and clinical features. TB burden in children worldwide and in Croatia, the risk of infection and disease, as well as disease characteristics, sources of infection in children, diagnostic difficulties, impact of HIV on pediatric tuberculosis, limits of BCG-vaccine and program implications are discussed in this paper. Children younger than 15 years account for 15%-20% of global TB burden, which is often associated with severe TB-related morbidity and mortality. Childhood TB is rarely sputum-smear positive on microscopy. That is probably the reason for the lower priority traditionally given to children by TB control programs compared to that of adult disease. Young children are at a high risk of rapid progression from infection to disease, reflecting recent transmission rather than secondary reactivation. Therefore, the pediatric burden potentially provides a useful measure of current transmission within a community and it is a good indicator of the efficacy of TB control achieved in a particular community. Strict contact tracing and use of preventive chemotherapy is important to reduce TB-related suffering of children. Untreated latent TB infection in children provides the seed of the epidemic for the next generation. Evidence of an adult TB index case is a clue for diagnosis of childhood TB in low-endemic countries. Prognosis of early detected and properly treated TB is excellent. Consequently, new diagnostic methods and treatment options are an imperative. Among HIV-coinfected children, the optimal timing for highly active antiretroviral therapy initiation and drug combinations that have minimal interactions with anti-TB drugs need to be further explored. The most effective vaccine, suitable even for HIV-infected children, remains the need for successful prevention at the global level. The Stop TB Strategy, which builds on the previous Directly Observed Treatment Short-Course Strategy (DOTS) developed by the World Health Organization, has a critical role in reducing the worldwide burden of the disease and thus in protecting children from infection and disease. The management of children with TB should be in line with the Stop TB Strategy, taking into consideration the particular epidemiology and clinical presentation of TB in children. In addition to reducing the burden of adult TB, attention to childhood nutrition and improvement of socioeconomic conditions of communities is likely to have an impact on TB transmission to children.     

Interactions Between Genetic Variants in Glucose Transporter Type 9 (SLC2A9) and Dietary Habits in Serum Uric Acid Regulation

Aim

To investigate possible interactions between genetic variants in glucose transporter type 9 (SLC2A9) gene and dietary habits in serum uric acid regulation.

Methods

Participants for this study were recruited from two isolated Croatian island communities of Vis (n = 918) and Korčula (n = 898). Three single nucleotide polymorphisms (SNP) from the SLC2A9 gene (rs1014290, rs6449213, rs737267) were correlated with dietary habits and uric acid.

Results

A significant decrease in uric acid levels was recorded with increasing consumption of milk, sour cream, duck and turkey, and eggs. The only significant interaction was found between potato consumption and rs737267 and a near-significant interaction was found between soft drinks and rs1014290 (interaction P = 0.068). Increased consumption of soft drinks interacting with the TT genotype at rs1014290 increased serum uric acid. No significant interactions were observed between food products consumption and rs6449213.

Conclusion

There is a certain extent of interaction between SLC2A9 and dietary patterns in serum uric acid determination. The metabolic effect of soft drinks seems to be determined by the underlying genotype of rs1014290.Gout is a disorder of purine metabolism that presents as inflammatory arthritis caused by urate crystallizing in joints following chronic hyperuricemia. It affects 1%-2% of the adult population in the Western world, especially elderly men. Diet and, more recently, genetic polymorphisms have been recognized as the most important factors causatively associated with serum uric acid levels and gout (1). High protein intake and purine-rich products, like meat and seafood, have been known to increase serum uric acid and the risk of gout, while vegetables rich in purine content showed no effect (2). On the other hand, the protective effect of certain foods has been identified. For example, dairy products, vitamin C, and coffee have been reported to decrease serum uric acid and prevalence of gout (1).Serum urate concentration is a highly variable trait among humans. It is greatly affected by environmental factors (diet), but shows high heritability of about 60% (3). Not surprisingly, genome-wide association studies identified genetic polymorphisms that substantially affect urate concentrations and gout. Polymorphisms in a transporter gene GLUT9 (SLC2A9) have been shown to explain 1.7%-5.3% of the variance in serum uric acid concentration (4,5). Recently, polymorphisms in 3 additional genes, URAT1 (SLC22CA12), ABCG2, and SLC17A3, have also been associated with uric acid concentrations and the risk of gout (6-8).SLC2A9 was first described as a glucose transporter and only later as a urate transporter. The study investigating whether glucose or fructose influenced urate transport in African clawed frog oocytes (Xenopus laevis) demonstrated that SLC2A9-mediated urate transport was facilitated by glucose and, to a lesser extent, fructose (9). We wanted to investigate if we could observe the same effect in vivo in humans and whether diet in general had a different impact on serum uric acid depending on the genetic background of an individual. To our knowledge, this is the first study on uric acid and gout that investigates genotype-environment interaction, more specifically, the interaction between previously reported genetic polymorphisms in the SLC2A9 gene and diet in humans.     

Longitudinal changes in PON1 activities, PON1 phenotype distribution and oxidative status throughout normal pregnancy

The purpose of the present study was to determine changes in plasma paraoxonase-1 activity (an indicator of paraoxonase phenotype) throughout normal pregnancy and its relationship with maternal oxidative stress status. The frequencies of the paraoxonase-1 phenotype in the studied population were determined using a two-substrate (paraoxon/diazoxon) activity method. As a parameter of oxidative stress status we measured the redox balance. Paraoxonase-1 activity significantly decreased at gestational week 32. In addition, the lipid profile was more atherogenic. Redox balance was significantly increased across gestational weeks. There were independent direct associations between maternal smoking habits before pregnancy, glucose concentrations and redox balance with PON1 activity in the third trimester. This study shows that pregnancy is followed by a decrease in PON1 activity and increased risk for development of cardiovascular diseases. We conclude that changes in paraoxonase-1 status during pregnancy are associated with maternal oxidative stress status and smoking habits.