BACKGROUND _ AIMS: @entity285 consumption is a major cause of @entity409 and contributes to a large proportion of @entity82 -related @entity204 worldwide. However, only a fraction of heavy consumers of @entity285 develop advanced @entity5881 ( @entity5881 ), so there are likely to be other risk factors. We investigated whether polymorphisms in the gene encoding @entity20501 ( @entity20501 ), previously shown to mediate @entity99 , were associated with the development of @entity5881 . METHODS: We isolated DNA from peripheral blood mononuclear cells (PBMCs) of 575 individuals with at-risk @entity285 consumption but no other risk factors for @entity409 ; all subjects were white Europeans who had consumed more than 80 grams @entity1068 per day. Of the subjects, 388 had @entity5881 (including, 268 with @entity82 and 74 with @entity99 ; mean age, 49 y; 72% male) and 187 had normal liver function with no biochemical or clinical evidence of @entity409 (controls; mean age, 42 y; 73% male). Select @entity20501 polymorphisms were genotyped using allelic discrimination. We also genotyped and measured expression of @entity20501 messenger RNA in PBMCs from individuals who were not heavy consumers of @entity285 . RESULTS: We used data from the HapMap project to identify 5 single-nucleotide polymorphisms (SNPs) that tag all the common haplotypes. When we looked for these SNPs in individuals with vs without @entity409 , 4 ( @entity69155 , @entity69156 , @entity69157 , and @entity69158 ) were associated with an increased risk of developing @entity5881 . We found that levels of @entity20501 messenger RNA and protein expressed were associated with an allele carried by PBMCs. Multivariate analysis confirmed that @entity69156 and @entity69158 were associated with an increased risk of @entity5881 . CONCLUSIONS: In a genetic analysis of heavy consumers of @entity285 , we associated 2 SNPS in @entity20501 with the development of @entity5881 . Although larger studies are required, this information could be used to determine the risk of individuals developing @entity5881 or to develop therapeutic agents.

Variants in the @entity20501 Gene Are Associated With Development of @entity409 in Heavy Consumers of XXXX .

@entity69157 :: ('rs732222', 'SNP') :: ['rs732222'] @entity69158 :: ('rs4794976', 'SNP') :: ['rs4794976'] @entity82 :: ('MESH:D005355', 'Disease') :: ['cirrhosis'] @entity5881 :: ('MESH:D008108', 'Disease') :: ['ALD', 'alcoholic liver disease'] @entity99 :: ('MESH:D056486', 'Disease') :: ['alcoholic hepatitis', 'liver injury'] @entity409 :: ('MESH:D008107', 'Disease') :: ['chronic liver disease', 'liver disease'] @entity69156 :: ('rs4239242', 'SNP') :: ['rs4239242'] @entity69155 :: ('rs3751093', 'SNP') :: ['rs3751093'] @entity20501 :: ('3965', 'Gene') :: ['LGALS9', 'galectin-9'] @entity285 :: ('D000431', 'Chemical') :: ['alcohol', 'Alcohol'] @entity204 :: ('MESH:D003643', 'Disease') :: ['deaths'] @entity1068 :: ('MESH:D000431', 'Chemical') :: ['ethanol']
@entity285 :: (D000431,Chemical) :: ['Alcohol']
