MBL2 gene variants coding for mannose-binding lectin deficiency are associated with increased risk of nephritis in Danish patients with systemic lupus erythematosus

N Tanha; L Troelsen; M-L From Hermansen; L Kjær; M Faurschou; P Garred; Susanne Jacobsen

doi:10.1177/0961203314536478

MBL2 gene variants coding for mannose-binding lectin deficiency are associated with increased risk of nephritis in Danish patients with systemic lupus erythematosus

N Tanha, L Troelsen, M-L From Hermansen, L Kjær, M Faurschou, P Garred, Susanne Jacobsen

Department of Clinical Medicine

11 Citations (Scopus)

Abstract

OBJECTIVES: Autoimmunity may in part result from deficiencies in the processing of apoptotic debris. As mannose-binding lectin (MBL) is involved in such processes, we hypothesized that the variants in the MBL2 gene resulting in MBL deficiency confer an increased risk of nephritis in systemic lupus erythematosus (SLE).

METHODS: A total of 171 SLE patients attending a Danish tertiary rheumatology referral center were included. Common variant alleles in exon 1 of the MBL2 gene (R52C, rs5030737; G54D, rs1800450; G57E, rs1800451) were genotyped. The normal allele and variant alleles are termed A and O, respectively. The follow-up period was defined as the time from fulfillment of the ACR 1987 classification criteria for SLE until the occurrence of an event (nephritis, end-stage renal disease (ESRD), or death) or end of follow-up. Cox regression analyses were controlled for gender, age and race.

RESULTS: During a median follow-up of 5.7 years, nephritis developed in 94 patients, and ESRD developed in 16 of these patients. Twenty-seven patients died. The distribution of the MBL2 genotypes A/A, A/O and O/O was 58%, 35% and 7.0%, respectively. Compared to the rest, O/O patients had 2.6 times (95% CI: 1.2-5.5) higher risk of developing nephritis, and their risk of death after 10 years was 6.0 times increased (95% CI: 1.0-36). MBL serum levels below 100 ng/ml were associated with a 2.0 (95% CI: 1.2-3.4; p = 0.007) increased risk of developing nephritis. ESRD and histological class of nephritis were not associated with MBL deficiency.

CONCLUSIONS: Genetically determined MBL deficiency was associated with development of nephritis in SLE patients, but not with histological class of nephritis or ESRD.

Original language	English
Journal	Lupus
Volume	23
Issue number	11
Pages (from-to)	1105-1111
Number of pages	7
ISSN	0961-2033
DOIs	https://doi.org/10.1177/0961203314536478
Publication status	Published - Oct 2014

Keywords

Adolescent
Adult
Aged
Alleles
Child
Denmark
Female
Follow-Up Studies
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Lupus Erythematosus, Systemic
Lupus Nephritis
Male
Mannose-Binding Lectin
Metabolism, Inborn Errors
Middle Aged
Proportional Hazards Models
Regression Analysis
Risk Factors
Young Adult

Access to Document

10.1177/0961203314536478

Cite this

@article{2a321cd84fa04850b8feef7d3dd1a048,

title = "MBL2 gene variants coding for mannose-binding lectin deficiency are associated with increased risk of nephritis in Danish patients with systemic lupus erythematosus",

abstract = "OBJECTIVES: Autoimmunity may in part result from deficiencies in the processing of apoptotic debris. As mannose-binding lectin (MBL) is involved in such processes, we hypothesized that the variants in the MBL2 gene resulting in MBL deficiency confer an increased risk of nephritis in systemic lupus erythematosus (SLE).METHODS: A total of 171 SLE patients attending a Danish tertiary rheumatology referral center were included. Common variant alleles in exon 1 of the MBL2 gene (R52C, rs5030737; G54D, rs1800450; G57E, rs1800451) were genotyped. The normal allele and variant alleles are termed A and O, respectively. The follow-up period was defined as the time from fulfillment of the ACR 1987 classification criteria for SLE until the occurrence of an event (nephritis, end-stage renal disease (ESRD), or death) or end of follow-up. Cox regression analyses were controlled for gender, age and race.RESULTS: During a median follow-up of 5.7 years, nephritis developed in 94 patients, and ESRD developed in 16 of these patients. Twenty-seven patients died. The distribution of the MBL2 genotypes A/A, A/O and O/O was 58%, 35% and 7.0%, respectively. Compared to the rest, O/O patients had 2.6 times (95% CI: 1.2-5.5) higher risk of developing nephritis, and their risk of death after 10 years was 6.0 times increased (95% CI: 1.0-36). MBL serum levels below 100 ng/ml were associated with a 2.0 (95% CI: 1.2-3.4; p = 0.007) increased risk of developing nephritis. ESRD and histological class of nephritis were not associated with MBL deficiency.CONCLUSIONS: Genetically determined MBL deficiency was associated with development of nephritis in SLE patients, but not with histological class of nephritis or ESRD.",

keywords = "Adolescent, Adult, Aged, Alleles, Child, Denmark, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Lupus Erythematosus, Systemic, Lupus Nephritis, Male, Mannose-Binding Lectin, Metabolism, Inborn Errors, Middle Aged, Proportional Hazards Models, Regression Analysis, Risk Factors, Young Adult",

author = "N Tanha and L Troelsen and {From Hermansen}, M-L and L Kj{\ae}r and M Faurschou and P Garred and Susanne Jacobsen",

note = "{\textcopyright} The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.",

year = "2014",

month = oct,

doi = "10.1177/0961203314536478",

language = "English",

volume = "23",

pages = "1105--1111",

journal = "Lupus",

issn = "0961-2033",

publisher = "SAGE Publications",

number = "11",

}

TY - JOUR

T1 - MBL2 gene variants coding for mannose-binding lectin deficiency are associated with increased risk of nephritis in Danish patients with systemic lupus erythematosus

AU - Tanha, N

AU - Troelsen, L

AU - From Hermansen, M-L

AU - Kjær, L

AU - Faurschou, M

AU - Garred, P

AU - Jacobsen, Susanne

N1 - © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

PY - 2014/10

Y1 - 2014/10

N2 - OBJECTIVES: Autoimmunity may in part result from deficiencies in the processing of apoptotic debris. As mannose-binding lectin (MBL) is involved in such processes, we hypothesized that the variants in the MBL2 gene resulting in MBL deficiency confer an increased risk of nephritis in systemic lupus erythematosus (SLE).METHODS: A total of 171 SLE patients attending a Danish tertiary rheumatology referral center were included. Common variant alleles in exon 1 of the MBL2 gene (R52C, rs5030737; G54D, rs1800450; G57E, rs1800451) were genotyped. The normal allele and variant alleles are termed A and O, respectively. The follow-up period was defined as the time from fulfillment of the ACR 1987 classification criteria for SLE until the occurrence of an event (nephritis, end-stage renal disease (ESRD), or death) or end of follow-up. Cox regression analyses were controlled for gender, age and race.RESULTS: During a median follow-up of 5.7 years, nephritis developed in 94 patients, and ESRD developed in 16 of these patients. Twenty-seven patients died. The distribution of the MBL2 genotypes A/A, A/O and O/O was 58%, 35% and 7.0%, respectively. Compared to the rest, O/O patients had 2.6 times (95% CI: 1.2-5.5) higher risk of developing nephritis, and their risk of death after 10 years was 6.0 times increased (95% CI: 1.0-36). MBL serum levels below 100 ng/ml were associated with a 2.0 (95% CI: 1.2-3.4; p = 0.007) increased risk of developing nephritis. ESRD and histological class of nephritis were not associated with MBL deficiency.CONCLUSIONS: Genetically determined MBL deficiency was associated with development of nephritis in SLE patients, but not with histological class of nephritis or ESRD.

AB - OBJECTIVES: Autoimmunity may in part result from deficiencies in the processing of apoptotic debris. As mannose-binding lectin (MBL) is involved in such processes, we hypothesized that the variants in the MBL2 gene resulting in MBL deficiency confer an increased risk of nephritis in systemic lupus erythematosus (SLE).METHODS: A total of 171 SLE patients attending a Danish tertiary rheumatology referral center were included. Common variant alleles in exon 1 of the MBL2 gene (R52C, rs5030737; G54D, rs1800450; G57E, rs1800451) were genotyped. The normal allele and variant alleles are termed A and O, respectively. The follow-up period was defined as the time from fulfillment of the ACR 1987 classification criteria for SLE until the occurrence of an event (nephritis, end-stage renal disease (ESRD), or death) or end of follow-up. Cox regression analyses were controlled for gender, age and race.RESULTS: During a median follow-up of 5.7 years, nephritis developed in 94 patients, and ESRD developed in 16 of these patients. Twenty-seven patients died. The distribution of the MBL2 genotypes A/A, A/O and O/O was 58%, 35% and 7.0%, respectively. Compared to the rest, O/O patients had 2.6 times (95% CI: 1.2-5.5) higher risk of developing nephritis, and their risk of death after 10 years was 6.0 times increased (95% CI: 1.0-36). MBL serum levels below 100 ng/ml were associated with a 2.0 (95% CI: 1.2-3.4; p = 0.007) increased risk of developing nephritis. ESRD and histological class of nephritis were not associated with MBL deficiency.CONCLUSIONS: Genetically determined MBL deficiency was associated with development of nephritis in SLE patients, but not with histological class of nephritis or ESRD.

KW - Adolescent

KW - Adult

KW - Aged

KW - Alleles

KW - Child

KW - Denmark

KW - Female

KW - Follow-Up Studies

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Genotype

KW - Humans

KW - Lupus Erythematosus, Systemic

KW - Lupus Nephritis

KW - Male

KW - Mannose-Binding Lectin

KW - Metabolism, Inborn Errors

KW - Middle Aged

KW - Proportional Hazards Models

KW - Regression Analysis

KW - Risk Factors

KW - Young Adult

U2 - 10.1177/0961203314536478

DO - 10.1177/0961203314536478

M3 - Journal article

C2 - 24850777

SN - 0961-2033

VL - 23

SP - 1105

EP - 1111

JO - Lupus

JF - Lupus

IS - 11

ER -

MBL2 gene variants coding for mannose-binding lectin deficiency are associated with increased risk of nephritis in Danish patients with systemic lupus erythematosus

Abstract

Keywords

Access to Document

Fingerprint

Cite this