Abstract Objective To study the association of polymorphisms of FokI rs2228570 in the vitamin D receptor (VDR) gene and TMPRSS6 rs855791 with cow's milk protein allergy (CMPA) in children.Methods Quantitative real-time PCR was used to analyze the single nucleotide polymorphisms of FokI rs2228570 in the VDR gene and TMPRSS6 rs855791 in 100 children with CMPA and 100 healthy children (control group). The multivariate logistic regression model was used to identify the risk factors for CMPA.Results There were significant differences in the frequencies of CC, CT, and TT genotypes of TMPRSS6 rs855791 between the CMPA and control groups (P=0.008), and the CMPA group had a significantly higher frequency of TT genotype. The multivariate logistic regression analysis showed that the children with TT genotype of rs855791 had an increased risk of CMPA (OR=3.473, P=0.011). However, there was no significant difference in the genotype distribution of FokI rs2228570 in the VDR gene between the two groups (P=0.686).Conclusions TMPRSS6 rs855791 polymorphism is associated with CMPA in children, and TT genotype may be the susceptible genotype of CMPA. FokI rs2228570 polymorphism is not associated with CMPA.
ZHANG Ye,GUO Yong,MA Jian et al. Association of FokI rs2228570 and TMPRSS6 rs855791 polymorphisms with cow's milk protein allergy in children[J]. CJCP, 2018, 20(8): 641-646.
ZHANG Ye,GUO Yong,MA Jian et al. Association of FokI rs2228570 and TMPRSS6 rs855791 polymorphisms with cow's milk protein allergy in children[J]. CJCP, 2018, 20(8): 641-646.
Alduraywish SA, Lodge CJ, Campbell B, et al. The march from early life food sensitization to allergic disease:a systematic review and meta-analyses of birth cohort studies[J]. Allergy, 2016, 71(1):77-89.
[2]
Einisman H, Reyes ML, Angulo J, et al. Vitamin D levels and vitamin D receptor gene polymorphisms in asthmatic children:a case-control study[J]. Pediatr Allergy Immunol, 2015, 26(6):545-550.
[3]
Cherayil BJ. Iron and immunity:immunological consequences of iron deficiency and overload[J]. Arch Immunol Ther Exp (Warsz), 2010, 58(6):407-415.
[4]
Nwaru BI, Hayes H, Gambling L, et al. An exploratory study of the associations between maternal iron status in pregnancy and childhood wheeze and atopy[J]. Br J Nutr, 2014, 112(12):2018-2027.
[5]
Oh S, Chung J, Kim M, et al. Antioxidant nutrient intakes and corresponding biomarkers associated with the risk of atopic dermatitis in young children[J]. Eur J Clin Nutr, 2010, 64(3):245-252.
[6]
Chambers JC, Zhang W, Li Y, et al. Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels[J]. Nat Genet, 2009, 41(11):1170-1172.
[7]
Pei SN, Ma MC, You HL, et al. TMPRSS6 rs855791 polymorphism influences the susceptibility to iron deficiency anemia in women at reproductive age[J]. Int J Med Sci, 2014, 11(6):614-619.
Jo J, Garssen J, Knippels L, et al. Role of cellular immunity in cow's milk allergy:pathogenesis, tolerance induction, and beyond[J]. Mediators Inflamm, 2014:1-10.
Topaloğlu N, Oğuz S, Sılan F, et al. Association of vitamin D receptor gene polymorphisms in children with atopic diseases[J]. Gene Ther Mol Biol, 2014, 16(1):55-60.
[12]
Wang C, Meynard D, Lin HY. The role of TMPRSS6/matriptase-2 in iron regulation and anemia[J]. Front Pharmacol, 2014, 5:114.
[13]
An P, Wu Q, Wang H, et al. TMPRSS6, but not TF, TFR2 or BMP2 variants are associated with increased risk of iron-deficiency anemia[J]. Hum Mol Genet, 2012, 21(9):2124-2131.
[14]
Nai A, Pagani A, Silvestri L, et al. TMPRSS6 rs855791 modulates hepcidin transcription in vitro and serum hepcidin levels in normal individuals[J]. Blood, 2011, 118(16):4459-4462.
[15]
Brigham EP, McCormack MC, Takemoto CM, et al. Iron status is associated with asthma and lung function in US women[J]. PLoS One, 2015, 10(2):e0117545.
[16]
Kay AB. Allergy and allergic diseases. First of two parts[J]. N Engl J Med, 2001, 344(1):30-37.
[17]
Sica A, Mantovani A. Macrophage plasticity and polarization:in vivo veritas[J]. J Clin Invest, 2012, 122(3):787-795.
[18]
Leung S, Holbrook A, King B, et al. Differential inhibition of inducible T cell cytokine secretion by potent iron chelators[J]. J Biomol Screen, 2005, 10(2):157-167.
[19]
Dostal A, Fehlbaum S, Chassard C, et al. Low iron availability in continuous in vitro colonic fermentations induces strong dysbiosis of the child gut microbial consortium and a decrease in main metabolites[J]. FEMS Microbiol Ecol, 2013, 83(1):161-175.
[20]
Molloy J, Allen K, Collier F, et al. The potential link between gut microbiota and IgE-mediated food allergy in early life[J]. Int J Environ Res Public Health, 2013, 10(12):7235-7256.
Allen KJ, Koplin JJ, Ponsonby AL, et al. Vitamin D insufficiency is associated with challenge-proven food allergy in infants[J]. J Allergy Clin Immunol, 2013, 131(4):1109-1116.
[23]
Silva CM, Silva SAD, Antunes MMC, et al. Do infants with cow's milk protein allergy have inadequate levels of vitamin D?[J]. J Pediatr (Rio J), 2017, 93(6):632-638.
[24]
Zmuda JM, Cauley JA, Ferrell RE. Molecular epidemiology of vitamin D receptor gene variants[J]. Epidemiol Rev, 2000, 22(2):203-217.
Despotovic M, Jevtovic Stoimenov T, Stankovic I, et al. Vitamin D receptor gene polymorphisms in Serbian patients with bronchial asthma:a case-control study[J]. J Cell Biochem, 2017, 118(11):3986-3992.
