Functional significance of single nucleotide polymorphisms in the lactase gene in diverse US patients and evidence for a novel lactase persistence allele at -13909 in those of European ancestry.
J Pediatr Gastroenterol Nutr
; 60(2): 182-91, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25625576
ABSTRACT
OBJECTIVES:
Recent data from mainly homogeneous European and African populations implicate a 140-bp region 5' to the transcriptional start site of LCT (the lactase gene) as a regulatory site for lactase persistence and nonpersistence. Because there are no studies of US nonhomogeneous populations, we performed genotype/phenotype analysis of the -13910 and -22018 LCT single nucleotide polymorphisms (SNPs) in New England children, mostly of European ancestry.METHODS:
Duodenal biopsies were processed for disaccharidase activities, RNA quantification by reverse transcription polymerase chain reaction (RT-PCR), allelic expression ratios by PCR, and genotyping and SNP analysis. Results were compared with clinical information.RESULTS:
Lactase activity and mRNA levels, and sucrase-to-lactase ratios of enzyme activity and mRNA, showed robust correlations with genotype. None of the other LCT SNPs showed as strong a correlation with enzyme or mRNA levels as did -13910. Data were consistent, with the -13910 being the causal sequence variant instead of -22018. Four individuals heterozygous for -13910T/C had allelic expression patterns similar to individuals with -13910C/C genotypes; of these, 2 showed equal LCT expression from the 2 alleles and a novel variant (-13909C>A) associated with lactase persistence.CONCLUSIONS:
The identification of -13910C/C genotype is likely to predict lactase nonpersistence, consistent with prior published studies. A -13910T/T genotype will frequently, but not perfectly, predict lactase persistence in this mixed European-ancestry population; a -13910T/C genotype will not predict the phenotype. A long, rare haplotype in 2 individuals with -13910T/C genotype but equal allele-specific expression contains a novel lactase persistence allele present at -13909.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
Lactase
/
População Branca
/
Duodeno
Limite:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
País/Região como assunto:
America do norte
Idioma:
En
Revista:
J Pediatr Gastroenterol Nutr
Ano de publicação:
2015
Tipo de documento:
Article