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preLekára.sk / Odborné časopisy / PLOS Genetics / 2011 - 4

GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32
and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell
Lymphoma

English version České info

Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological

malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A

previous genome-wide association study has established a marker, rs10484561 in

the human leukocyte antigen (HLA) class II region on 6p21.32 associated with

increased FL risk. Here, in a three-stage genome-wide association study,

starting with a genome-wide scan of 379 FL cases and 791 controls followed by

validation in 1,049 cases and 5,790 controls, we identified a second independent

FL–associated locus on 6p21.32, rs2647012

(ORcombined = 0.64,

Pcombined = 2×10−21)

located 962 bp away from rs10484561 (r2<0.1 in controls). After

mutual adjustment, the associations at the two SNPs remained genome-wide

significant (rs2647012:
ORadjusted = 0.70,

Padjusted = 4×10−12;

rs10484561:
ORadjusted = 1.64,

Padjusted = 5×10−15).

Haplotype and coalescence analyses indicated that rs2647012 arose on an

evolutionarily distinct haplotype from that of rs10484561 and tags a novel

allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up

analysis of the top 6 FL–associated SNPs in 4,449 cases of other NHL

subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma

(ORcombined = 1.36,

Pcombined = 1.4×10−7).

Our results reveal the presence of allelic heterogeneity within the HLA class II

region influencing FL susceptibility and indicate a possible shared genetic

etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA

class II region plays a complex yet important role in NHL.

Vyšlo v časopise: GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma. PLoS Genet 7(4): e32767. doi:10.1371/journal.pgen.1001378
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001378

Souhrn

Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological

malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A

previous genome-wide association study has established a marker, rs10484561 in

the human leukocyte antigen (HLA) class II region on 6p21.32 associated with

increased FL risk. Here, in a three-stage genome-wide association study,

starting with a genome-wide scan of 379 FL cases and 791 controls followed by

validation in 1,049 cases and 5,790 controls, we identified a second independent

FL–associated locus on 6p21.32, rs2647012

(ORcombined = 0.64,

Pcombined = 2×10−21)

located 962 bp away from rs10484561 (r2<0.1 in controls). After

mutual adjustment, the associations at the two SNPs remained genome-wide

significant (rs2647012:
ORadjusted = 0.70,

Padjusted = 4×10−12;

rs10484561:
ORadjusted = 1.64,

Padjusted = 5×10−15).

Haplotype and coalescence analyses indicated that rs2647012 arose on an

evolutionarily distinct haplotype from that of rs10484561 and tags a novel

allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up

analysis of the top 6 FL–associated SNPs in 4,449 cases of other NHL

subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma

(ORcombined = 1.36,

Pcombined = 1.4×10−7).

Our results reveal the presence of allelic heterogeneity within the HLA class II

region influencing FL susceptibility and indicate a possible shared genetic

etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA

class II region plays a complex yet important role in NHL.

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2011 Číslo 4
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