ALLELIC ASSOCIATION STUDY BETWEEN COLLAGEN TYPE-1 (COLIA1AND COLIA2) POLYMORPHISMS AND ALCOHOL LIVER-DISEASE

The amount and duration of excessive alcohol compsumption leading to l iver injury are uncertain. While most heavy drinkers show evidence of fatty liver, only a minority develops features of overt disease (cirrh osis or hepatitis). Genetic factors associated to an increased suscept ibility to these disorders have long time been suspected. Given that t ype I collagen is markedly increased in advanced liver cirrhosis, the human procollagen type alpha-1 (COLIA1) and alpha-2 (COLIA2) genes hav e been proposed as ''candidate'' genes in studies of genetic predispos ition of the disease. The aim of this work was to analyze polymorphism s for the type I procollagen genes from alcoholic patients with and wi thout cirrhosis, to test the hypothesis that these variants are relate d (and possibly contribute) to a predisposition to develop alcohol-ind uced liver damage. Seventy- four Mexican subjects who acknowledged hav ing drank 80 or more g of ethanol/day for at least 15 years were studi ed. Diagnosis or exclusion of alcohol liver disease (cirrhosis) was es tablished by history, physical examination, biochemical tests, ultraso und and, in some cases, biopsy of the liver. Genotype analysis of thre e chosen regions of the type I procollagen genes (two in COLIA1, and o ne in COLIA2) containing polymorphic variants, were studied after PCR amplification. Observed allele and genotype frequencies for the polymo rphisms analyzed were not statistically differerent among groups. Inte restingly, the frequency for a common allele for the Rsal/COLIA1 syste m was higher in alcoholics compared with healthy subjects. In summary, the polymorphisms studied do not seem to be associated to a higher ri sk or susceptibility of alcohol liver damage. We cannot rule out that other loci, not explored herein, may contain molecular variants in lin kage disequilibrium with nearby mutations modifying biosynthesis or st ructure of the type I collagen, affected directly or indirectly after an alcohol challenge.