Polymorphisms in mitochondrial genes encoding complex I subunits are maternal factors of voluntary alcohol consumption in the rat.

. This function resides in complex I of the respiratorychain and its variation is linked to genes transmittedthrough the maternal line. The aim of this study was toidentify the genetic basis for the difference in thereoxidation of NADH in these nondrinker (UChA) anddrinker (UChB) rats.Methods Seven mitochondrial genes and twochromosome X genes encoding complex I subunitsfrom rats of both lineages were amplified from liverDNA and sequenced.Results The UChA and UChB rat lines differ in their Nd2,Nd4, Nd5 and Nd6 mitochondrial genes and in the encodedproteins. Most noteworthy are ND2 and ND4 whose aminoacid variations lead to changes in three-dimensionalstructure models. The ND2 proteins also differ in thenumber of predicted transmembrane domains. The Nd1and Nd3 genes have silent substitutions, whereas Nd4Land the exonic sequences of the nuclear genes Ndufa1 andNdufb11 show no differences between the UChA andUChB lines.Conclusion Amino acid variations in fourcomplex I subunits encoded in the mitochondrialgenome may contribute to explain the differencesbetween UChA and UChB rats in their capacity toreoxidize NADH and in their alcohol intake, suggestingthat mitochondrial genes may constitute maternalfactors of alcoholism. Pharmacogenetics and Genomics19:528–537