Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: Summary

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: SummaryIt could be argued that organ involvement in sarcoidosis is often subclinical, and it may be important to detect both clinical and subclinical organ involvement when classifying sarcoidosis phenotypes. This argument will only be settled when a connection is made between the phenotypic expression of sarcoidosis and genetic patterns. Until this is connection is made, this study used reasonable clinical criteria to detect organ involvement. buy claritin online
The time period over which these data were collected was also not uniform. However, for most sibling pairs, data were collected over many years, so that it is likely that a true estimate of prevalence and phenotypic expression was determined. For example, spirometric data were compared over a median of 5 years, and 85% of the affected sibling pairs had > 2 years of follow-up after diagnosis. This study demonstrated more involvement of every organ than the large ACCESS study of US sarcoidosis patients, but patients in ACCESS were enrolled within 6 months of diagnosis and extrathoracic manifestations may not be apparent near the time of diagnosis. Finally, our results could have been affected by missing data. However, for all clinical parameters except spirometry, the percentage of missing data was < 12.2%. In the case of spirometry, in which there was missing data in slightly more than one fourth of the cases, there were no significant differences in any other measured clinical parameter between those with and without spirometry data.
For most organ systems, we had medical record data on > 90% of patients, and our sample exceeded 200 pairs, which provided adequate statistical power even with missing data. Nevertheless, the prevalence of organ involvement for some organs was so low that it was difficult to reach meaningful statistical conclusions. Finally, sibling relationships were not ascertained randomly, and an examination of disease course in probands compared with their affected siblings showed a significant greater severity of disease in the former. This tendency toward ascertaining index cases with severe disease could bias the overall sibling sample in terms of how well it represents all sibling pairs affected with sarcoidosis.
In conclusion, the phenotypic expression of sarcoidosis sibling pairs shows little concordance in terms of organ involvement, severity of pulmonary involvement, or clinical course. One exception was a modest sibling concordance of liver and ocular involvement. The fact that the few associations found were weak may suggest that sibling phenotypic variation is related to the timing, duration, or dose of environmental exposures. Possibly, specific genes affect the phenotypic expression of sarcoidosis only in the presence of specific environmental exposures. Another possibility is that the genes for sarcoidosis development and phenotypic expression of the disease are distinct. Future studies of the SAGA study population will explore these possibilities.

This entry was posted in Sarcoidosis and tagged genetics, phenotype, sarcoidosis, sibling.