Acute chest syndrome is associated with single nucleotide polymorphism-defined beta globin cluster haplotype in children with sickle cell anaemia.

Genetic diversity at the human ß-globin locus has been implicated as a modifier of sickle cell anaemia (SCA) severity. However, haplotypes defined by restriction fragment length polymorphism sites across the ß-globin locus have not been consistently associated with clinical phenotypes. To define the genetic structure at the ß-globin locus more thoroughly, we performed high-density single nucleotide polymorphism (SNP) mapping in 820 children who were homozygous for the sickle cell mutation (HbSS). Genotyping results revealed very high linkage disequilibrium across a large region spanning the locus control region and the HBB (ß-globin gene) cluster. We identified three predominant haplotypes accounting for 96% of the ß(S) -carrying chromosomes in this population that could be distinguished using a minimal set of common SNPs. Consistent with previous studies, fetal haemoglobin level was significantly associated with ß(S) -haplotypes. After controlling for covariates, an association was detected between haplotype and rate of hospitalization for acute chest syndrome (ACS) (incidence rate ratio 0·51, 95% confidence interval 0·29-0·89) but not incidence rate of vaso-occlusive pain or presence of silent cerebral infarct (SCI). Our results suggest that these SNP-defined ß(S) -haplotypes may be associated with ACS, but not pain or SCI in a study population of children with SCA.

Trends in venous thromboembolism among pregnancy-related hospitalizations, United States, 1994-2009.

OBJECTIVE: The purpose of this study was to evaluate national trends in the rate of pregnancy-related hospitalizations for venous thromboembolism (VTE) from 1994-2009 and to estimate the prevalence of comorbid conditions among these hospitalizations. STUDY DESIGN: An estimated 64,413,973 pregnancy-related hospitalizations among women 15-44 years old were identified in the 1994-2009 Nationwide Inpatient Sample. Trends in VTE-associated pregnancy hospitalizations were evaluated with the use of variance-weighted least squares regression. Chi-square tests were used to assess changes in prevalence of demographics and comorbid conditions, and multivariable logistic regression was used to evaluate the likelihood of VTE during the study period after adjustment for comorbid conditions. Antepartum, delivery, and postpartum hospitalizations were evaluated separately and reported in 4-year increments. RESULTS: From 1994-2009, there was a 14% increase in the rate of overall VTE-associated pregnancy hospitalizations; antepartum and postpartum hospitalizations with VTE increased by 17% and 47%, respectively. Between 1994-1997 and 2006-2009, the prevalence of hypertension and obesity doubled among all VTE-associated pregnancy hospitalizations; significant increases in diabetes mellitus and heart disease were also noted. A temporal increase in the likelihood of a VTE diagnosis in pregnancy was observed for antepartum hospitalizations from 2006-2009 when compared with 1994-1997 (adjusted odds ratio, 1.62; 95% confidence interval, 1.48-1.78). CONCLUSION: There has been an upward trend in VTE-associated pregnancy hospitalizations from 1994-2009 with concomitant increases in comorbid conditions. Clinicians should have a heightened awareness of the risk of VTE among pregnant women, particularly among those with comorbid conditions, and should have a low threshold for evaluation in women with symptoms or signs of VTE.

Increased risk of venous thromboembolism is associated with genetic variation in heme oxygenase-1 in Blacks.

BACKGROUND: Venous thromboembolism (VTE) affects as many as 1 in 1000 individuals in the United States. Although Blacks are disproportionately affected by VTE, few genetic risk factors have been identified in this population. The inducible heme oxygenase-1 (HMOX1) gene encodes a key cytoprotective enzyme with anti-inflammatory, antioxidant and anticoagulant activity acting in the vascular system. A (GT)(n) microsatellite located in the promoter of the HMOX1 gene influences the level of response. METHODS AND RESULTS: Using the Genetic Attributes and Thrombosis Epidemiology (GATE) study, we examined the association between HMOX1 repeat length and VTE events in 883 Black and 927 White patients and matched controls. We found no association between HMOX1 genotypes and VTE in Whites. However, in Black patients, carrying two long (L) alleles (≥ 34 repeats) was significantly associated with provoked (odds ratio (OR) 1.86, 95% confidence interval (CI): 1.19-2.90) or recurrent (OR 3.13, 95% CI: 1.77-5.53) VTE events. CONCLUSIONS: We have demonstrated for the first time an association between genetic variation in HMOX1, and VTE in Blacks. Our results support a key role for the heme oxygenase system in protecting patients at increased risk for thrombosis and suggest a potential mechanism for targeted screening and intervention.

Particulate pollutants and racial/ethnic disparity in feto-infant morbidity outcomes.

We sought to assess the association between air particulate pollutants and feto-infant morbidity outcomes across racial/ethnic subgroups. This is a retrospective cohort study from 2000 through 2007 based on three linked databases: (1) The Florida Hospital Discharge database; (2) The vital statistics records of singleton live births in Florida; (3) Air pollution and meteorological data from the Environmental Protection Agency. Using computerized mathematical modeling, we assigned exposure values of the air pollutants of interest (PM(2.5), PM(10) and the PM coarse fraction [PM(10) - PM(2.5)]) to mothers over the period of pregnancy based on Euclidean minimum distance from the air pollution monitoring sites. The primary outcomes of interest were: low birth weight, very low birth weight, preterm birth, very preterm birth, and small for gestational age (SGA). We used adjusted odds ratios to approximate relative risks. We observed increased risk for overall feto-infant morbidity outcome in women exposed to any of the three particulate pollutants (values above the median). Exposed women had increased odds for low birth weight, very low birth weight and preterm birth with the greatest risk being that for very low birth weight (AOR = 1.27, 95% CI = 1.08-1.49). Black women exposed to any particulate pollutant had the greatest odds for all the morbidity outcomes, most pronounced for very low birth weight (AOR = 3.32, 95% CI = 2.56-4.30). Environmental particulate pollutants are associated with adverse feto-infant outcomes among exposed women, especially blacks. Black-white disparity in adverse fetal outcomes is widened in the presence of these pollutants, which provide a target for intervention.