Low Zinc May Indicate Potential Breast-Feeding Problems

A new study provides an important step toward identifying breast-fed infants at risk for severe zinc deficiency. Identifying mothers with abnormally low levels of zinc in breast milk may enable to more quickly determine those more likely to have trouble breast-feeding.

The protein ZnT2 transports zinc in specific tissues, including the mammary glands, where zinc is necessary for growth of mammary glands and function of mammary epithelial cells and secretion pathways. In previous studies, Shannon L. Kelleher, associate professor at Penn State University’s College of Medicine (Hershey, PA, USA) and colleagues found that ZnT2 is critical for secreting zinc into breast milk and women who have ZnT2 mutations have substantially lower milk zinc levels, leading to severe zinc deficiency in exclusively breast-fed infants. Also, ZnT2 deletion in mice altered milk composition and profoundly impaired the ability of mice to successfully nurse their offspring.

Now the researchers have found that ZnT2 genetic variation resulting in either loss or gain of function may be common and in some cases is associated with indicators of poor breast function. Of 54 breast-feeding women, 36% had at least one non-synonymous single nucleotide polymorphism (SNP) in ZnT2 and the genetic variation was associated with abnormal levels of zinc in their breast milk. 12 previously unknown variants of ZnT2 were identified in the participants, and 5 of these variants were statistically associated with abnormal zinc levels in breast milk. "We had no idea that genetic variation in ZnT2 would be so common," said Prof. Kelleher.

Among the 36% of breast-feeding women found to have at least one genetic variant in ZnT2, all had an abnormally low or high level of zinc in breast milk. However, abnormal zinc levels did not automatically imply a problem with ZnT2, indicating that other factors remain to be identified.

The participants were sorted into 4 groups according to breast milk zinc levels. In the group with the lowest zinc levels, researchers identified ZnT2 variants in 79% of the women; in the group with the highest levels, 29% had ZnT2 variants. Importantly, among the subjects with normal milk zinc levels, no variants in ZnT2 were detected.

The researchers also examined the milk for ratio of sodium to potassium (Na/K) as a known indicator of breast dysfunction, including infection and inflammation of the breast. 12% of women had the most common ZnT2 variant, T288S, and had a significantly higher Na/K ratio compared with women with no variation in ZnT2. Another 9% of women with a different, less common ZnT2 variant, D103E, had a higher Na/K ratio than women with no ZnT2 variation, although this was not significant due to the low number of women in the study with this variant.

Together these observations point to ZnT2 variation as a modifier of breast function and zinc levels in breast milk as a potential indicator of deficient lactation. Further research is needed to better understand how genetic variation affects milk zinc levels and breast function.

The study, by Alam S et al., was published in the December 2015 issue of the Journal of Mammary Gland Biology and Neoplasia.

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