title: Fas promoter polymorphisms: genetic predisposition to sarcoidosis in African-Americans.
abstract: Apoptosis may perpetuate some forms of inflammation. Of the apoptotic pathway proteins, Fas is particularly overexpressed in sarcoidosis. We hypothesized that Fas promoter single nucleotide polymorphisms (SNPs) contribute to the development and severity of sarcoidosis. Associations of known Fas promoter SNPs (-670, -690 and -1377) and deduced haplotypes with sarcoidosis and sarcoidosis severity were evaluated using matched case-control (n = 656 pairs) and case-comparison (n = 656) studies, respectively, using conditional logistic regression. Hardy-Weinberg equilibrium was confirmed for all three polymorphisms in African-Americans (AA), and for the -670 and -1377 in whites. Genotype and allele frequencies were significantly different between whites and AA. Race-stratified analysis revealed that a common haplotype, -1377G/-690T/-670G, was associated with sarcoidosis [odds ratio (OR) = 1.78, P = 0.05] only in AA. The haplotype -1377G/-690C/-670A was negatively associated with sarcoidosis (OR = 0.39, P = 0.03) only in AA. In conclusion, the consistency of these findings suggests that Fas promoter genetic variants may be related to sarcoidosis disease risk in AA.
authors.affiliation: Merck Research Laboratories, Upper Gwynedd, PA, USA.
authors.forename: Y S
authors.initials: YS
authors.lastname: Wasfi
authors.forename: L J
authors.initials: LJ
authors.lastname: Silveira
authors.forename: A
authors.initials: A
authors.lastname: Jonth
authors.forename: J E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: T
authors.initials: T
authors.lastname: Fingerlin
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: C E
authors.initials: CE
authors.lastname: Parsons
authors.forename: P
authors.initials: P
authors.lastname: Lympany
authors.forename: K
authors.initials: K
authors.lastname: Welsh
authors.forename: R M
authors.initials: RM
authors.lastname: du Bois
authors.forename: L S
authors.initials: LS
authors.lastname: Newman
authors.forename: L A
authors.initials: LA
authors.lastname: Maier
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012507:Sarcoidosis / Q000453:epidemiology / Q000235:genetics*; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics; D019014:fas Receptor / Q000235:genetics*
chemical_list: C491901:FAS protein, human; D019014:fas Receptor