Lactose intolerance is a common digestive condition where individuals experience discomfort after consuming milk products. This condition arises from the body’s inability to fully break down lactose, a sugar present in milk and dairy. The prevalence of lactose intolerance varies significantly across different human populations, suggesting an underlying biological basis for this digestive difference.
The Role of Lactase
Lactose is a disaccharide, meaning it is a sugar composed of two smaller sugar units, glucose and galactose. When consumed, lactose travels to the small intestine, where it needs to be broken down into these simpler units for absorption into the bloodstream. This breakdown is facilitated by an enzyme called lactase. Lactase is produced by specialized cells lining the small intestine, particularly in the brush border. The primary function of the lactase enzyme is to cleave the chemical bond linking glucose and galactose in lactose. Once separated, these monosaccharides, glucose and galactose, can be readily absorbed through the intestinal wall.
If there is insufficient lactase activity, undigested lactose continues its journey to the large intestine. In the large intestine, gut bacteria ferment the unabsorbed lactose, leading to the production of gases and drawing water into the bowel, which results in symptoms such as bloating, abdominal pain, and diarrhea.
The Lactase Gene and Its Regulation
The human body’s ability to produce the lactase enzyme is controlled by a specific gene known as LCT. This LCT gene is located on chromosome 2 and provides the instructions for synthesizing the lactase enzyme. While the LCT gene itself codes for the enzyme, its activity is largely governed by a distinct regulatory region. This regulatory region is not within the LCT gene itself but is found upstream, within an adjacent gene called MCM6. The MCM6 gene acts as a genetic switch for the LCT gene.
In most mammals, including a significant portion of the human population, the LCT gene naturally downregulates its activity after the weaning period. This reduction in lactase production is the ancestral human condition, reflecting a time when milk consumption typically ceased after infancy. Variations within the MCM6 regulatory region dictate whether this reduction in lactase production occurs or if the LCT gene remains active into adulthood. These variations fundamentally determine an individual’s ability to digest lactose beyond infancy.
Genetic Variations and Global Patterns
Specific genetic variations within the MCM6 regulatory region are strongly associated with lactase persistence, which is the continued production of lactase into adulthood. One of the most well-studied single nucleotide polymorphisms (SNPs) is C/T-13910. Other influential SNPs include G/A-22018, T/G-13907, and C/G-14010, each contributing to the sustained expression of the LCT gene. These variants prevent the natural decline in lactase production, allowing individuals to digest lactose throughout their lives.
The global distribution of these lactase persistence variants is not uniform, reflecting human evolutionary history and the independent development of dairy farming in different populations. For instance, the C/T-13910 variant is highly prevalent in Northern European populations, where dairy farming has been a long-standing practice for thousands of years. Other variants are more common in specific populations in Africa and the Middle East, indicating separate evolutionary adaptations to a dairy-rich diet. Conversely, populations with a limited history of dairy consumption, such as many East Asian, Southeast Asian, and some Native American groups, exhibit a much lower frequency of these lactase persistence alleles.
Types of Lactose Intolerance
While the genetic basis primarily explains the most common form of lactose intolerance, it is important to distinguish its types. Primary lactose intolerance, also known as adult-onset lactase non-persistence, is the most prevalent form and is directly linked to the genetic variations discussed. In this type, the LCT gene naturally reduces its activity after childhood, leading to a diminished capacity to digest lactose. This form accounts for the vast majority of cases seen globally.
Secondary lactose intolerance arises from damage to the small intestine, which temporarily impairs lactase production. Conditions such as celiac disease, Crohn’s disease, or acute gastroenteritis can damage the intestinal lining and reduce lactase enzyme levels. This type is often reversible, with lactase activity potentially recovering once the underlying intestinal damage is resolved. Congenital lactase deficiency is an extremely rare genetic condition where individuals are born with little to no lactase activity. This severe form manifests immediately after birth, requiring specialized dietary management from infancy.