Genome-wide linkage and association studies have uncovered variants associated with sarcoidosis, a multi-organ granulomatous inflammatory disease. African ancestry may influence disease pathogenesis since African Americans are more commonly affected by sarcoidosis. Therefore, we conducted the first sarcoidosis genome-wide ancestry scan using a map of 1,384 highly ancestry informative single nucleotide polymorphisms genotyped on 1,357 sarcoidosis cases and 703 unaffected controls self-identified as African American. The most significant ancestry association was at marker rs11966463 on chromosome 6p22.3 (ancestry association risk ratio (aRR)= 1.90; p=0.0002). When we restricted the analysis to biopsy-confirmed cases, the aRR for this marker increased to 2.01; p=0.00007. Among the eight other markers that demonstrated suggestive ancestry associations with sarcoidosis were rs1462906 on chromosome 8p12 which had the most significant association with European ancestry (aRR=0.65; p=0.002), and markers on chromosomes 5p13 (aRR=1.46; p=0.005) and 5q31 (aRR=0.67; p=0.005), which correspond to regions we previously identified through sib pair linkage analyses. Overall, the most significant ancestry association for Scadding stage IV cases was to marker rs7919137 on chromosome 10p11.22 (aRR=0.27; p=2×10−5), a region not associated with disease susceptibility. In summary, through admixture mapping of sarcoidosis we have confirmed previous genetic linkages and identified several novel putative candidate loci for sarcoidosis.

Background-African American patients suffer disproportionately from uncontrolled asthma. Treatment with an inhaled corticosteroid (ICS) is considered first-line therapy for persistent asthma.

The synthesis of vitamin D is altered by the granulomatous inflammation of sarcoidosis leading to increased production of 1, 25-dihydroxyvitamin D. Mounting evidence suggests that vitamin D is an immunomodulating hormone that inhibits both antigen presentation by cells of the innate immune system, and the cytokine release and proliferation of Th1 cells. These and other extraskeletal health benefits have led to an increase in vitamin D assessment and pharmacological supplementation in the general population. This review highlights the altered synthesis and general immunomodulating properties of vitamin D with a special emphasis on known interactions with sarcoidosis. In addition, the assessment of vitamin D nutritional status, its pharmacological supplementation, and the management of bone health in patients with sarcoidosis are reviewed.

Summary Background Active vitamin D metabolite, 1, 25-dihydroxyvitamin D, has pleomorphic effects on both innate and acquired immunity. Sarcoid granuloma derived 1, 25-dihydroxyvitamin D leads to hypercalcemia, but the association of 1, 25-dihydroxyvitamin D with the clinical phenotype of the disease is currently unknown. Objective To determine the relationship between serum 1, 25-dihydroxyvitamin D levels and the degree of sarcoidosis disease chronicity. Design Serum 1, 25-dihydroxyvitamin D levels were measured and associated with sarcoidosis activity and phenotypes as assessed by Sarcoidosis Severity Score and Sarcoidosis Clinical Activity Classification respectively. Results Fifty nine patients were recruited with 44% having a sub-acute onset, and the chronic disease phenotype. There was no significant difference in serum 1, 25-dihydroxyvitamin D levels by chest radiograph stage (p = 0.092) nor did the levels correlate with the Sarcoidosis Severity Score (r = −0.16; p = 0.216). Serum 1, 25-dihydroxyvitamin D levels were associated with patients requiring repeated regimens of systemic immunosuppressive therapy or >1 year of therapy (SCAC Class 6). Increasing quartiles of serum 1, 25-dihydroxyvitamin D level was associated increased odds of the chronic phenotype (OR 1.82, 95% CI, 1.11, 2.99, p = 0.019). The majority (71%) of the patients with levels >51 pg/mL required chronic immunosuppressive therapy as defined by SCAC class 6. Conclusions In patients with sarcoidosis, elevated 1, 25-dihydroxyvitamin D levels are associated with chronic treatment needs.

Study Objectives While sarcoidosis generally inflicts a greater morbidity on African-American compared with Caucasian patients, no studies have examined whether racial differences exist in the intensity of the histologic hallmark of sarcoidosis, noncaseating granulomas. Design and Setting The study was conducted as a retrospective case series in a tertiary referral center. Patients The study included 187 patients with histopathologic confirmation of sarcoidosis by trans- and/or endobronchial biopsy between July 1991 and December 2001. Measurements and Results Granuloma density was the average number of granulomas per biopsy piece on the slide with the most intense granulomatous inflammation at fourfold magnification. Overall, African-American patients had a twofold greater median granuloma density than Caucasians (p = 0.005). In a negative binomial multivariate model, radiographic pattern had the strongest association with granuloma density, with Scadding stage II and III patients having adjusted granuloma densities of 60% (p = 0.005) and 105% (p = 0.0001) higher than stage I patients. In the specific-tissue types, radiographic stage–adjusted granuloma densities in African-American patients were 49% greater in bronchial tissue (p = 0.03), but only a 27% greater in alveolar tissue (p = 0.51). Conclusions A greater granuloma density in bronchiolar lung tissue of African-American sarcoidosis patients may explain racial differences in diagnostic yield by lung biopsy and disease severity at diagnosis. This association persists even after controlling for Scadding radiographic stage, a measure of disease severity strongly associated with granuloma density.