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Print version ISSN 1807-5932

Clinics vol.65 no.12 São Paulo  2010 



LCT-22018G>A single nucleotide polymorphism is a better predictor of adult-type hypolactasia/lactase persistence in Japanese-Brazilians than LCT-13910C>T



Rejane Mattar; Maria do Socorro Monteiro; Joyce Matie Kinoshita da Silva; Flair José Carrilho

Hospital das Clínicas da Faculdade de Medicina da USP - Gastroenterology. Av. Dr. Eneas de Carvalho Aguiar 255, 9° andar sala 9159, Cerqueira Cesar, São Paulo, SP, Brazil, CEP 05403-000. Tel. 11-30696150, fax. 11-30697830. Email: Tel.: 55 11 3069-6150




Adult type hypolactasia, the genetically programmed down-regulation of lactase enzyme activity in the intestinal wall after weaning, is a common condition worldwide, except for in northwestern Europe, where the prevalence is less than 10%. Lactose intolerant individuals complain of abdominal cramps, bloating, distention, flatulence and diarrhea after milk or lactose-containing food ingestion.1

The diagnosis of adult-type hypolactasia can be achieved by a hydrogen breath test that is cumbersome and provokes symptoms, or more recently, using a genetic approach.2 Lactase persistence and adult-type hypolactasia have been associated with the LCT-13910>T and LCT-22018G>A polymorphisms in introns 13 and 9, respectively, of the minichromosome maintenance type 6 gene (MCM6) upstream of the LCT locus in several populations.3

In Brazil, the lactase persistence allele, LCT-13910T, was found in approximately 43% of both white (European descent) and brown (European and African descent), and 20% of black (African descent) Brazilians, but was absent in all Japanese-Brazilians studied.4 Recent epidemiological data regarding lactose intolerance/hypolactasia are lacking in Japan. This lack of information may be because of the relative rarity of symptoms; it has been shown that, although 92% of tested subjects were lactase deficient, only 2% were milk intolerant and 13% were lactose intolerant.5

Recent evidence in northern China suggests that LCT-22018G>A, rather than LCT-13910C>T, LCT-13907C>G, LCT-13915T>G, or LCT-14010G>C, matched the lactase persistence phenotype.6 Therefore, the purpose of this study was to ascertain whether LCT-22018G>A would also be a predictor of lactase persistence in Japanese-Brazilians.



This study was approved by the local Ethics Committee. The study population consisted of 56 Japanese-Brazilians with the LCT-13910CC genotype according to a previously described genotyping technique,4 with a mean age of 47.1 + 17.6 years. Seventeen (30.4%) men gave written informed consent to participate.

DNA was extracted from leukocytes. Primers 5'-AACAGGCACGTGGAGGAGTT-3' (position 18261-18280) and 5'-CCCACCTCAGCCTCTTGAGT-3' (position 18708-18689), Accession number AY220757, spanning the LCT-22018 region, were used in a polymerase chain reaction (PCR) with Premium Taq DNA polymerase (Invitrogen, São Paulo, Brazil) and 2.5 mM MgCl2. Amplification was performed in 38 cycles at 95°C for 1 min, 67°C for 1 min, and 72°C for 1 min. The PCR product was digested with HhaI, resulting in one fragment of 448 bp (the AA genotype), two fragments of 264 and 184 bp (the GG genotype) and three fragments of 448, 264, and 184 bp (the GA genotype), which were visualized on a 2% agarose gel stained with ethidium bromide, as has been previously described by Büning et al.7



Among the 56 Japanese-Brazilians who were previously genotyped as LCT-13910CC (hypolactasia),4 3 (5.4%) had the LCT-22018GA genotype associated with lactase persistence (Fig. 1), and 53 (94.6%) had the LCT-22018GG genotype associated with hypolactasia (Table 1).





The incidence of lactase deficiency gradually increases with age from 3 years, and approximately 90% of all normal Japanese adults are lactase-deficient.8 Among Japanese-Brazilians, 100% had lactose malabsorption;9 therefore, these values are in accordance with lactose malabsorption in Japanese people who have been diagnosed by the hydrogen breath test.

In Brazilians, both the LCT-13910C>T allele2 and the LCT-22018G>A allele10 have been associated with lactase persistence phenotypes. As such, genetic analysis for Japanese-Brazilians should include an assessment for the LCT-22018G>A allele, as the LCT-13910C>T polymorphism is already routinely performed for hypolactasia/lactase persistence diagnosis.2



The LCT-22018G>A allele is a better predictor of lactase persistence in Japanese-Brazilians than the LCT-13910C>T allele.



1. Mattar R, Mazo DFC. Intolerância à lactose: mudança de paradigmas com a biologia molecular. Rev Assoc Med Bras. 2010;56:230-6, doi: 10.1590/S0104-42302010000200025.         [ Links ]

2. Mattar R, Monteiro MS, Villares CA, Santos AF, Carrilho FJ. Single nucleotide polymorphism C/T-13910, located upstream of the lactase gene, associated with adult-type hypolactasia: validation for clinical practice. Clin Biochem. 2008;41:628-30, doi: 10.1016/j.clinbiochem.2008.01.006.         [ Links ]

3. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Javerlã I. Identification of a variant associated with adult-type hypolactasia. Nat Genet. 2002;30:233-7, doi: 10.1038/ng826.         [ Links ]

4. Mattar R, Monteiro MS, Villares CA, Santos AF, Silva JMK, Carrilho FJ. Frequency of LCT-23920C>T single nucleotide polymorphism associated with adult-type hypolactasia/lactase persistence among Brazilians of different ethnic groups. Nutr J. 2009;8:46, doi: 10.1186/1475-2891-8-46.         [ Links ]

5. Kondo T, Liu F, Toda Y. Milk is a useful test meal for measurement of small bowel transit time. J Gastroenterol. 1994;29:715-20, doi: 10.1007/BF02349276.         [ Links ]

6. Xu L, Sun H, Zhang X, Wang J, Sun D, Chen F, et al. The -22018A allele matches the lactase persistence phenotype in northern Chinese populations. Scand J Gastroenterol. 2010;45:168-174, doi: 10.3109/00365520903414176.         [ Links ]

7. Büning C, Ockenga J, Krüger S, Jurga J, Baier P, Dignass A,et al. The C/C-13910 and G/G-22018 genotypes for adult-type hypolactasia are not associated with inflammatory bowel disease. Scand J Gastroenterol. 2003; 38:538-42.         [ Links ]

8. Nose O, Iida Y, Kai H, Harada T, Ogawa M, Yabuuchi H. Breath hydrogen test for detecting lactose malabsorption in infants and children. Arch Dis Child. 1979;54:436-40, doi: 10.1136/adc.54.6.436.         [ Links ]

9. Sevá-Pereira A, Beiguelman B. Primary lactose malabsorption in healthy Brazilian adult caucasoid, negroid and mongoloid subjects. Arq Gastroenterol. 1982;19:133-8.         [ Links ]

10. Bernardes-Silva CF, Pereira AC, da Mota GFA, Krieger JE, Laudanna AA. Lactase persistence/non-persistence variants, C/T_13910 and G/A_22018, as a diagnostic tool for lactose intolerance in IBS patients. Clin Chim Acta. 2007;386:7-11, doi: 10.1016/j.cca.2007.07.012.         [ Links ]




CLINICS 2010;65(12):1399-1400

Replace: RejaneMattar, Maria Monteiro para Maria do Socorro Monteiro, Joyce Matie Silva para Joyce Matie Kinoshita da Silva, FlairCarrilhopara Flair Jose Carrilho

For: Rejane Mattar, Maria do Socorro Monteiro, Joyce Matie Kinoshita da Silva, Flair Jose Carrilho

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