LongevityMap Gene

Gene details

HGNC symbol: HLA-DRB1
Aliases: SS1; DRB1; HLA-DRB; HLA-DR1B
Common name: major histocompatibility complex, class II, DR beta 1
Description: HLA-DRB1 belongs to the HLA class II beta chain paralogs. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa. It is encoded by 6 exons. Exon one encodes the leader peptide; exons 2 and 3 encode the two extracellular domains; exon 4 encodes the transmembrane domain; and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1 alleles have been described and typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. DRB1 is expressed at a level five times higher than its paralogs DRB3, DRB4 and DRB5. DRB1 is present in all individuals. Allelic variants of DRB1 are linked with either none or one of the genes DRB3, DRB4 and DRB5. There are 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9. [provided by RefSeq, Jul 2008]
Cytogenetic Location: 6p21.32
UCSC Genome Browser: View 6p21.32 on the UCSC genome browser
OMIM: 142857
Ensembl: ENSG00000196126
UniProt/Swiss-Prot: 2B13_HUMAN
Entrez Gene: 3123
UniGene: 534322
1000 Genomes: 1000 Genomes

Homologs in model organisms

Danio rerio: mhc2dab
Danio rerio: si:dkey-33b17.3
Danio rerio: zgc:103700
Danio rerio: mhc2dbb
Danio rerio: mhc2dab
Danio rerio: zgc:103700
Danio rerio: si:zfos-2070c2.3
Danio rerio: mhc2dab
Danio rerio: si:busm1-228j01.6
Danio rerio: si:busm1-228j01.4
Danio rerio: mhc2dab
Danio rerio: si:ch73-158p21.3
Danio rerio: si:busm1-194e12.12
Danio rerio: si:busm1-228j01.4
Danio rerio: si:busm1-104n07.3
Mus musculus: H2-Eb2
Mus musculus: H2-Eb1
Rattus norvegicus: RT1-Db2
Rattus norvegicus: RT1-Db1

Studies (6)

Significant/Non-significant: 4/2

Study 1

Longevity Association

Population

Study Design

The longevous groups included two independent cohorts totalling 533 centenarians and 163 nonagenarian siblings. Control group included 2950 subjects.

Conclusions

DR7 frequency was elevated in longevous men and DR13 frequency was increased in centenarians. DR11's influence on longevity displayed a significant interaction with sex, with an increase in women from longevous sibships. HLA-DR homozygotes were more frequent in centenarians than in controls.

Indentifier

Reference

Study 2

Longevity Association

Non-significant

Population

Study Design

A total of 71 healthy elders were studied, age ranged from 80 to 96 years (mean 86.2 years). The control samples were obtained from 99 young (from 21 - 54 years; mean 35.2 years) healthy individuals unrelated to elders.

Conclusions

An increased frequency of HLA-DRB1*11 was found in elderly women whereas this allele was not present in elderly males, though no significant differences between age groups were observed

Indentifier

Reference

Study 3

Longevity Association

Population

Italian (Palermo)

Study Design

77 centenarians and 299 healthy controls were genotyped for HLA-DRB1 and 44 centenarians and 57 healthy controls for KIR receptors=HLA ligands

Conclusions

An HLA allele (DRB1*18) was associated with longevity. No significant association between successful aging and KIR gene content was observed in this Sicilian population.

Indentifier

Reference

Study 4

Longevity Association

Population

Study Design

82 centenarians (64 females, 100- 106y, average 101.1y), 20 nonagenarians (16 females, 90- 99y, average 96.5y) and 159 healthy adults (81 females, 18- 88y, average 58.1y) were genotyped for associations with longevity involving 80 HLA antigen phenotypes.

Conclusions

Extremely low frequency of HLA-DRw9 and an increased frequency of DR1 were found in centenarians and nonagenarians populations. HLA-DRw9 was a risk factor for longevity (corrected P = 0.0001). HLA-DR1 was a favourable factor for longevity (corrected P = 0.00367). High frequency of HLA-DRw9 and low frequency of DR1 are known to be associated with autoimmune or immune deficiency diseases.

Indentifier

Reference

Study 5

Longevity Association

Population

Japanese (Okinawa)

Study Design

Polymorphisms in Okinawan centenarians were analyzed

Conclusions

DRB1*1401 allele was significantly increased in the centenarians while DRB1*0101 and DRB1*1201 alleles were slightly decreased

Indentifier

Reference

Study 6

Longevity Association

Non-significant

Population

Study Design

10 alleles were examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females), and a control group with 105 randomly selected, matched for geographical distribution healthy controls aged 25-53 years (40 male and 65 female)

Conclusions

The most frequent HLADRB1 alleles in elderly Bulgarians were DRB111 and DRB113. The most frequent haplotypes in elderly Bulgarians compared to the controls were DRB111-DQB103 and DRB113-DQB106, though this was not statistically significant after correcting for multiple testing.

Indentifier

Reference