TY  - CHAP
M1  - Book, Section
TI  - Genetic Polymorphism of Intestinal Lactase Activity in Adult Humans
A1  - Swallow, Dallas M.
A1  - Hollox, Edward J.
A2  - Valle, David L.
A2  - Antonarakis, Stylianos
A2  - Ballabio, Andrea
A2  - Beaudet, Arthur L.
A2  - Mitchell, Grant A.
Y1  - 2019
N1  - 10.1036/Ommbid.386
T2  - The Online Metabolic and Molecular Bases of Inherited Disease
AB  - Dietary  lactose  is  hydrolyzed  by  the  enzyme  lactase  which  is  located  in  the  brush  border  of  small  intestinal  enterocytes.  Lactase  activity  is  high  during  infancy,  when  milk  is  the  main  nutrient.  As  in  other  mammals,  lactase  activity  declines  after  the  weaning  phase  in  the  majority  of  humans  and  remains  low  throughout  life  (phenotype:  lactase  nonpersistence,  also  known  as  restriction  or  adult-type  hypolactasia;  MIM  223100).  In  other  healthy  humans,  lactase  activity  persists  at  a  high  level  (phenotype:  lactase  persistence).  Subjects  with  lactase  nonpersistence  have  a  low  lactose  digestion  capacity  (low  LDC);  those  with  lactase  persistence  can  hydrolyze  large  amounts  of  lactose  (high  LDC).  The  adult  lactase  phenotypes  can  be  diagnosed  through  small-intestinal  biopsy  or  lactose-tolerance  tests.Family  studies,  measurement  of  relative  lactase  activity,  and  a  study  of  lactose  digestion  in  twins  show  that  the  lactase  phenotypes  are  genetically  determined  and  can  be  explained  by  a  Mendelian  system  of  two  autosomal  alleles.  The  lactase  persistence  allele  is  dominant  to  the  lactase  nonpersistence  (or  restriction)  allele:  the  individuals  with  low  LDC  are  homozygous  for  the  nonpersistence  allele.The  distribution  of  the  lactase  phenotypes  in  human  populations  is  highly  variable.  In  most  tropical  and  subtropical  countries  and  in  all  East  Asian  populations,  lactase  nonpersistence  is  predominant.  In  the  Old  World,  lactase  persistence  predominates  in  only  two  human  population  groups:  northwestern  Europeans  and  milk-dependent  nomads  of  the  Afro-Arabian  desert  zone.  Natural  selection  in  favor  of  the  lactase  persistence  gene  due  to  improved  utilization  of  animal  milk  in  the  nutrition  of  older  children  and  adults  with  high  LDC  is  a  likely  cause  of  the  unusual  lactase  phenotype  distribution  in  Europeans  and  Afro-Arabian  nomads.The  role  of  lactase  nonpersistence  in  irritable  bowel  syndrome  in  adults  and  osteoporosis  in  postmenopausal  women  and  the  role  of  lactase  persistence  in  promoting  coronary  heart  disease  and  premature  cataract  are  controversial.  However,  the  genetically  determined  downregulation  of  lactase  expression  may  contribute  to  malabsorption  and  abdominal  complaints,  particularly  in  young  children.A  number  of  nucleotide  polymorphisms  have  been  detected  both  in  the  coding  and  noncoding  regions  of  the  LCT  gene.  These  polymorphisms  are  associated  with  one  another  to  form  very  few  haplotypes  in  Europeans  and  lactase  persistence  is  associated  with  a  particular  haplotype  (A).  Studies  on  the  expression  of  lactase  mRNA  transcripts  that  made  use  of  these  polymorphisms  as  markers  have  demonstrated  that  a  genetic  change  in  a  cis-acting  regulatory  element  is  likely  to  be  responsible  for  this  polymorphism  in  lactase  activity,  at  least  in  Europeans.A  CT  polymorphism  at  −13910  is  strongly  associated  with  persistence/nonpersistence  in  Finns  and  other  Europeans  and  may  be  the  causal  change  because  the  presence  of  the  *TThis  chapter  is  derived  and  updated  from  Gebhard  Flatz  in  the  7th  edition  of  this  work.  allele  causes  enhancement  of  transcription  in  vitro  and  increases  binding  of  a  transcription  factor  Oct1.  The  −13910*T  allele  forms  part  of  a  very  extended  (more  than  500  kb)  A  haplotype.  This  polymorphism  however  does  not  explain  lactase  persistence  in  all  sub-Saharan  Africans  nor  in  Bedouins.In  Africans,  several  additional  mutations  have  been  identified  in  the  vicinity  of  −13910,  two  of  which  are  statistically  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
M3  - doi: 10.1036/Ommbid.386
Y2  - 2024/04/24
UR  - ommbid.mhmedical.com/content.aspx?aid=1181421469
ER  -