Beta-Casein A2A2

Milk protein variants

Milk is a food that is part of humans diets and casein is the main protein in milk.

Milk proteins can be divided in two main fractions: about 25% are whey proteins and not protein nitrogen compounds like urea; while 75 % are casein proteins, the most important since are one of the main compound involved in cheese production. The casein proteins are divided into 5 classes, one of which is Beta-Casein, that is about 36% of total casein.

Beta caseina


In general, the proteins are single-chain of Amino acid (229 in the case of Beta-Casein) and the sequence of them are regulated by DNA. In nature is possible to find several variants of the same protein, that can differ for substitution of only 1 or 2 amino acids.

Beta-casein variants

In the case of Beta-casein are known 13 variants, but only A1 and A2 variants are frequent in the main dairy cattle breeds used for intensive milk production.

The B variant is the less common one, the A3 and the C variants are rare, the variant I derives instead from a mutation of the variant A2 and normally has low frequencies. The variant E was found only in the Italian Piemontese breed while the remaining variants were never found in European cattle breeds. (Massella E., 2017).

The difference between the two variants is in position 67 of the chain, of the amino acid Histidine in the case of A1 and Proline in the A2.

The original variant seems to be A2 but with a mutation occurred about 5000 years ago, start to be present in the dairy cattle population the variant A1. Due to the selection, this last became the most frequent in Holstein Friesian population.

Furthermore, the two variants A1 and A2 differ, as mentioned, above in amino acid position 67 with histidine (CAT) for A1 and proline (CCT) for A2 (difference of a single nucleotide). This single nucleotide polymorphism caused a conformational change in the secondary structure of the expressed β-casein protein.

It has also been seen that the A2 variant is more comparable to the human Beta casein in terms of digestive breakdown (Clarke A., 2014).

Beta-Casein A2 and cheese production

The beta-casein variants (in particular A1, A2 and B) have received much attention from the scientific community due to their influence on the technological properties of milk and on human health. (Massella E., 2017)

Finally, the variants of beta-casein play an important role in the yield/quality of the cheese and their concentration is positively associated with the good properties of milk rennet.

It must be remembered, however, that everything is always due to the correlation between the different genotypes of the different caseins.

In this regard, there are several groups of researchers who are trying to understand, increasingly, the different correlations between the different genotypes.

New developments: Beta-Casein A2 and human health

As is well known since 2003, after a study conducted in New Zealand on the benefit to human health that who would consume milk with beta-casein A2A2, in some countries of Oceania and England, there has been a growing interest in the topic, coming to the marketing of milk containing only Beta-casein A2A2.

The most frequently observed variants of β-casein as mentioned are A1 and A2.

Beta-casein A2 has been shown to have beneficial health effects.

It should be remembered, however, that some scientific research in the past produced documentation that asserted that this particular type of milk induced a markedly lower lactose intolerance in consumers and also suggested a lower incidence of diseases such as diabetes, cardiovascular diseases, various intolerances, etc...

Research in this regard is still ongoing and the battle is still on between those in favour and against these arguments.

Production and sale of A2A2 milk

Today, cow's milk A2 or without the A1 variant is commercially available in a number of countries, including Australia, the United Kingdom, the United States, New Zealand and the Netherlands, and is widely promoted as beneficial for people who suffer from intolerances with milk. The formula for newborns containing casein A2 is now marketed in China and Australia and is commercially promoted as more delicate on the infant's digestive system. (Brooke-Taylor S., 2017)


Genetic management for produce milk A2A2

The production of Beta-casein is controlled by only one gene, like other proteins in the milk example k-casein. Depend on the genotype, the cow will produce milk with only beta-casein A1 or A2 or a mixture of A1 and A2, if the animal has a genotype "A1A1"or "A2A2" o "A1A2", respectively.
A possible strategy could be to fixing the gene A2 in the population, removing step by step the A2 gene using bulls A2A2 or A1A2 checking with DNA test the daughters.
Intermizoo started a selective program for increase A2 gene frequency in the population. Here we provide a list of bulls with A2 gene.


In these sections you can find the A2A2 bulls available at our centre:

Holstein Proven

Holstein Genomic




Clarke A., Trivedi M. (2014). Bovine beta casein variants: Implications to human nutrition and health. IPCBEE, 67, 11–17. doi:

Massella E., Piva S., Giacometti F., Liuzzo G., Zambrini A.V., Serraino A.(2017, September 29). Evaluation of bovine beta casein polymorphism in two dairy farms located in northern Italy. Italian Journal of Food Safety, 6. doi:10.4081/ijfs.2017.6904

Brooke-Taylor S., Dwyer K., Wooford K., Kost N. (2017, September 1). Systematic Review of the Gastrointestinal Effects of A1 Compared with A2 β-Casein. Advances in Nutrition, 739-748. Tratto da




Facebook icon
Google icon

Intermizoo S.p.A. | Sede Sociale: Via Po 21 - 35135 - Padova |Tel.: 049 8724757 Fax: 049 8724868
Email: Posta Certificata: | Cod.Fisc. e Registro Imprese di Padova 00338110273 - N.133655 R.E.A di PD | P.I. 00867200289