Galactose-deficient IgA1 in African Americans with IgA nephropathy: serum levels and heritability.
OBJECTIVE
Serum levels of galactose-deficient IgA1 (Gd-IgA1) are elevated and heritable in Caucasian and Asian patients with IgA nephropathy (IgAN), but have not been characterized in African Americans (AA). Our objective was to determine whether serum Gd-IgA1 levels are increased in AA patients with IgAN and whether this is a heritable trait in this group.


METHODS
Blood and urine samples were obtained from 18 adult and 11 pediatric AA patients with biopsy-proven IgAN and from 34 of their first-degree relatives. Healthy controls included 150 Caucasian adults, 65 AA adults, 45 Caucasian children, and 49 AA children. Serum total IgA and Gd-IgA1 levels were measured in patients and controls. Significant differences between patient and control groups for serum total IgA, Gd-IgA1, and ratio of Gd-IgA1/total IgA were determined by the Mann-Whitney U test. Heritability was calculated using SOLAR.


RESULTS
After stratifying by age, 7 of 11 pediatric and 9 of 18 adult AA patients with IgAN had serum Gd-IgA1 levels above the 95th percentile for age-appropriate AA controls. For first-degree relatives, the serum Gd-IgA1 level was >95th percentile for 1 of 8 when the patient's level was <95th percentile and 12 of 26 when the patient's level was >95th percentile (P = 0.116, Fisher exact test). Heritability was 0.74 (P = 0.007).


CONCLUSIONS
Serum levels of Gd-IgA1 are often elevated in AA patients with IgAN and their first-degree relatives. Thus, aberrant IgA1 glycosylation is a heritable risk factor for IgAN in African Americans.
Hastings
M Colleen
MC
Children's Foundation Research Center at Le Bonheur Children's Medical Center, Memphis, TN 38103-2893, USA.
Moldoveanu
Zina
Z
Julian
Bruce A
BA
Novak
Jan
J
Sanders
John T
JT
McGlothan
Kim R
KR
Gharavi
Ali G
AG
Wyatt
Robert J
RJ
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005690:Galactose / Q000097:blood* / Q000172:deficiency; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D006031:Glycosylation; D040941:Heredity; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation; D055815:Young Adult
D015415:Biomarkers; D007070:Immunoglobulin A; D005690:Galactose