Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene.

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8 x 10(-5)), establishing a novel phenotype for this genetic variant.

Postpartum plasma exchange as adjunctive therapy for severe acute fatty liver of pregnancy.

Acute fatty liver of pregnancy (AFLP) is a rare disease of progressive hepatic insufficiency and secondary systemic compromise that poses significant fetal-maternal risk. Plasma exchange (PEX) is an effective bridge therapy to sustain liver function and enable hepatocellular regeneration to occur in nonpregnant patients following acute decompensation of a chronic liver disease or while awaiting liver transplantation. The application of PEX for patients with AFLP is a novel concept; since 1988 we have utilized postpartum PEX (PPEX) as adjunctive medical therapy for six patients with severe AFLP. Before PPEX initiation, four patients had signs and symptoms of encephalopathy, three required ventilatory support, five had advanced liver insufficiency, and all six were developing renal failure. PPEX was initiated 2-8 days following delivery and repeated (two to four times, mean = 3) at 24-48-h intervals thereafter. All patients responded with composite clinical (symptoms/signs) and laboratory improvement; the average length of hospitalization following final PPEX for five of six patients was 7 days. No significant PPEX-related complications occurred. PPEX utilization in patients with severe AFLP may enhance maternal recovery by preventing secondary sequelae from hepatic insufficiency until spontaneous healing can occur. Further study appears to be indicated to validate a role for PPEX as supportive therapy for puerperal patients with AFLP suffering multiorgan failure.

Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies.

White blood cell count (WBC) is an important clinical marker that varies among different ethnic groups. African Americans are known to have a lower WBC than European Americans. We surveyed the entire genome for loci underlying this difference in WBC by using admixture mapping. We analyzed data from African American participants in the Health, Aging, and Body Composition Study and the Jackson Heart Study. Participants of both studies were genotyped across >or= 1322 single nucleotide polymorphisms that were pre-selected to be informative for African versus European ancestry and span the entire genome. We used these markers to estimate genetic ancestry in each chromosomal region and then tested the association between WBC and genetic ancestry at each locus. We found a locus on chromosome 1q strongly associated with WBC (p < 10(-12)). The strongest association was with a marker known to affect the expression of the Duffy blood group antigen. Participants who had both copies of the common West African allele had a mean WBC of 4.9 (SD 1.3); participants who had both common European alleles had a mean WBC of 7.1 (SD 1.3). This variant explained approximately 20% of population variation in WBC. We used admixture mapping, a novel method for conducting genetic-association studies, to find a region that was significantly associated with WBC on chromosome 1q. Additional studies are needed to determine the biological mechanism for this effect and its clinical implications.

Unusual skin lesions in chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a relatively rare, heterogeneous syndrome classified as a myelodysplastic syndrome according to the French-American-British classification system. The patient's presenting symptom was a pigmented skin nodule that, although common for cases of acute monoblastic leukemia, is peculiar for CMML. This case should increase awareness of the inclusion of CMML in the differential diagnosis of a discolored nodule and highlight the clinicopathologic considerations and therapeutic challenges consistent with the diagnosis of CMML.