Single nucleotide polymorphisms and microsatellite alleles of tumor necrosis factor alpha and interleukin-10 genes and the risk of advanced chronic alcoholic liver disease.
BACKGROUND
Only a minority of ethanol abusers develop advanced chronic alcoholic liver disease (CALD). In CALD there is a imbalance between TNF alpha and IL-10, which may be modulated by several polymorphisms at both genetic loci. Our aim has been to elucidate the possible relation between these polymorphisms and the risk of CALD.


METHODS
147 patients with advanced CALD and 355 healthy controls (all white Spaniards) were included. TNF alpha biallelic single nucleotide polymorphisms (SNP) at positions -238, -308, and -376 and IL-10 biallelic SNP at positions -597, - 824, and - 1087 were investigated by polymerase chain reaction (PCR) amplification and dot blot hybridization. Moreover, polymorphic microsatellites TNFa, TNFb, IL-10.R and IL-10.G were investigated in a multiplex PCR and alleles were estimated in an automatic sequencer.


RESULTS
No differences were found in the distribution of any of the studied polymorphisms, except by an excess of the haplotype formed by the allele 11 of the microsatellite IL-10.G and the GCC arrangement of the SNPs at the promoter of IL-10 gene in patients (15.7 vs. 8.24%, odds ratio: 2.08, 95% C.I. = 1.31-3.31).


CONCLUSIONS
The studied polymorphisms at TNF alpha and IL-10 genetic loci are not clearly related to the risk of CALD. The excess of G11-GCC haplotype found in CALD patients needs independent confirmation.
Ladero
José M
JM
Department of Gastroenterology, Hospital Clínico San Carlos, Medical School, Complutense University, Madrid, Spain. jladero@hcsc.insalud.es
Fernández-Arquero
Miguel
M
Tudela
José I
JI
Agúndez
José A G
JA
Díaz-Rubio
Manuel
M
Benítez
Julio
J
de la Concha
Emilio G
EG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D004247:DNA / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008108:Liver Diseases, Alcoholic / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004247:DNA