(齐康网) Drumm and colleagues (Oct. 6 issue)identifiedsequence variants in the TGF{beta}
1 gene as genetic modifiers of lungdisease in cystic fibrosis. TGF{beta}
1 is encoded on chromosome 19q13,4.5 Mbp from the CFM1 locus that confers a risk of meconiumileus.We scanned this region on 19q13 with use of single-nucleotidepolymorphisms (SNPs) and microsatellites in a cohort of siblingpairs homozygous for the {Delta}
F508 mutation with extreme clinicalphenotypesfor a modulator of disease severity. Neither thetwo TGF{beta}
1 SNPs (–509 and codon 10)nor the microsatelliteD19S112 at CFM1was associated with disease severity in ourcohort.866
Interrogation of the region between TGF{beta}
1 and CFM1 by four microsatellites,however, revealed a significant transmission disequilibriumin clinically discordant sibling pairs (a peak at D19S197, P=0.003),suggesting a modulation of factors acting in trans(Figure 1).The region contains the CEACAM gene family encoding cell-adhesionmolecules involved in the binding of pathogens and the regulationof differentiation, angiogenesis, and cancer. The TGF{beta}
1–CEACAMregion apparently contains at least one clinically relevantgenetic modifier of cystic fibrosis.
(文章出处：《新英格兰医学杂志》)齐康网
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