Genetic test for lactose intolerance

Lactose intolerance is defined as the inability of the body to digest lactose which leads to various gastrointestinal issues. Lactose is a sugar found in milk and many people are not able to digest it. Milk is a very nutritious food and contains micronutrients, carbohydrates and a fair amount of calcium, but some of us are intolerant to lactose and thus are unable to digest milk without experiencing diarrhea, bloating and abdominal cramps. Lactose is a disaccharide that is abundant in mammalian milk and essential for the nourishment of newborn infants. It is hydrolyzed by the intestinal brush-border enzyme, lactase, into absorbable sugars, namely glucose and galactose. In most infants, intestinal lactase activity is maximal during the perinatal period; however, after 2–12 years of age, two distinct groups emerge, ie, a “lactase non-persistence” group with low lactase activity (hypolactasia) and a “lactase-persistence” group of individuals who retain their neonatal level of lactase activity into adulthood.

Genetics of lactose intolerance

LCT gene

The LCT gene provides instructions for making an enzyme called lactase. This enzyme helps to digest lactose, a sugar found in milk and other dairy products.

Types of lactose intolerance

Congenital lactase deficiency or lactose intolerance in infants is caused by mutations in the LCT gene. Congenital lactase deficiency is a severe gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. Congenital lactase deficiency is one of the approximately 30 rare recessive disorders that are relatively common in Finland. In patients with congenital lactase deficiency, Koukkanen et al. 2006, identified 5 distinct mutations in the coding region of the LCT gene. In 27 of 32 patients (84%), they found homozygosity for a nonsense mutation, 4170T-A (Y1390X; 603202.0001), designated 'Fin(major).' In the other patients, they identified compound heterozygosity. The data demonstrated that, in contrast to adult-type hypolactasia (lactose intolerance) caused by a variant of the regulatory element, the severe infancy type represents the outcome of mutations affecting the structure of the protein with inactivation of the enzyme

Primary hypolactasia, or primary lactase deficiency, is genetic, only affects adults, and is caused by the absence of a lactase persistence allele. In individuals without the lactase persistence allele, less lactase is produced by the body over time, leading to hypolactasia in adulthood.

Secondary hypolactasia or secondary lactase deficiency, also called acquired hypolactasia or acquired lactase deficiency, is caused by an injury to the small intestine. This form of lactose intolerance can occur in both infants and lactase persistent adults and is generally reversible. It may be caused by acute gastroenterites, celiac disease, Crohn’s disease,ulcerative colitis, chemotherapy, intestinal parasites, or other environmental causes.

Only the genetic test can differentiate between primary and secondary lactose intolerance

The difference between genetically determined primary and secondary lactose intolerance is of great therapeutic importance because for patients with the primary form of lactose intolerance the only possible treatment options are a lactose-free diet or a diet low in lactose, or else to take lactase preparations for life. For patients with a secondary form of lactose intolerance, however, this treatment is only necessary until the intestinal epithelium has regenerated, following clarification of the cause and treatment of the underlying disease. A lifelong lactose-free diet is not necessary in the case of secondary lactose intolerance. 

Two LCT variants were associated with lactase persistence.A polymorph variant, LCT-13910C>T, in intron 13 of the MCM6 gene that is 13,910 bp from the initiation codon of LCT, demonstrated a complete association, while the LCT-22018G>A variant in intron 9 of MCM6 gene upstream of the LCT locus 22,018 bp was strongly, but not completely, associated.

The frequency of lactose intolerance ranges from 2% in Scandinavia to 20–40% in white populations in Central Europe and the United States, and increases to 53% among Mexican Americans to about 80% in blacks and to almost 100% in Southeast Asian populations. Studies have revealed that lactase persistence (LP), is a phenotype unique to humans. These genetic changes emerged relatively recently in the last 10,000 years within some populations. This coincides with the transition from nomadic to agricultural lifestyles when cattle domestication and milk/dairy food became common. In northern Europe, the GG genotype of the rs4988235 SNP in and the CC genotype of the rs182549 SNPwere identified as causal for lactose intolerance. In North Africa and the Middle East, a different set of alleles are associated with lactose intolerance: CC for rs145946881, AA for rs41380347 and GG for rs41525747.

The discovery of lactase-persistence alleles prompted use of genetic tests for diagnosis of lactase non-persistence by PCR restriction fragment length polymorphism, PCR real time ,and Pyrosequencing? technology.Compared with the lactose hydrogen breath test, the genetic test is a simple, noninvasive, and more comfortable examination that does not provoke symptoms of lactose intolerance and is less cumbersome,with easy transfer of a swab sample to the laboratory. 

References

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