Analysis of the NRAMP1 Gene Implicated in Iron Transport: Association with Multiple Sclerosis and Age Effects

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

“…A similar situation occurs between alleles 3 and 5, which are also distinguishable from each other by RsaI digestion. 24,44 Allele 5 was found in low frequencies in Scots, the German and Afrikaners. In other words, accurate genotyping of the promoter (GT) n polymorphism requires both fragment sizing and RsaI digestion, as has been demonstrated in the present study and in other studies.…”

“…On a global scale, the (GT) 9 allele has a frequency range of 0.65-0.75 in Afrikaners, 24 African Americans 25 and Caucasians (including the Swedish, 45 Latvians 22 and Columbians 19 ), and of 0.80-0.90 in Africans and Asians (including Chinese, Koreans, 21 Vietnamese, 46 Indians 47 and the Japanese 17,23 ). The (GT) 10 allele (or allele 2) ranks second in frequency (0.10-0.35), while the classical (GT) 11 allele (or allele 1) is usually the least frequent (o0.05).…”

“…In other words, accurate genotyping of the promoter (GT) n polymorphism requires both fragment sizing and RsaI digestion, as has been demonstrated in the present study and in other studies. 24,44 For markers SLC2 and SLC3, the minor alleles had a frequency of about 0.09 in Chinese ( Table 1). The minor allele frequencies had a range of 0.10-0.20 in Asians, 21,42,46,47 Africans 14 and African Americans, 25 while they varied between 0.25 and 0.35 in Caucasians.…”

“…18,19 In addition, the SLC11A1 gene also appears associated with autoimmune inflammatory diseases, for example, rheumatoid arthritis (RA) in Canadian Caucasians and Koreans, juvenile rheumatoid arthritis in Latvians, inflammatory bowel disease (IBD) in the Japanese, multiple sclerosis (MS) in South African Caucasians and sarcoidosis in African Americans. [20][21][22][23][24][25] However, some linkage studies failed to demonstrate linkage of the gene to these diseases. Two family-based linkage studies in West and South Africans and in Brazilians showed that a marker close to SLC11A1 (the microsatellite D2S1471), but not SLC11A1 itself, had a weak linkage to tuberculosis.…”

Ramp-ing up allergies: Nramp1 (Slc11a1), macrophages and the hygiene hypothesis

“…Polymorphisms in the genomic region of human NRAMP1 are associated with the risk of atopy in BCG-vaccinated children [23]. Moreover, the Nramp1 gene is involved in several other diseases of deregulated immunity: a polymorphism in the promoter region of NRAMP1 has been associated with inflammatory bowel disease [24], rheumatoid arthritis [25], multiple sclerosis [26] and type 1 diabetes mellitus [27].…”