Analysis of PLA2R1 and HLA-DQA1 sequence variants in Japanese patients with idiopathic and secondary membranous nephropathy

• Published in: Clinical and experimental nephrology Vol. 22; no. 2; pp. 275 - 282
• Main Authors: Kaga, Hajime, Komatsuda, Atsushi, Omokawa, Ayumi, Okuyama, Shin, Mori, Kensuke, Wakui, Hideki, Takahashi, Naoto
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01-04-2018; Springer Nature B.V
• Subjects: Adult; Aged; Asian Continental Ancestry Group - genetics; Case-Control Studies; Deoxyribonucleic acid; DNA; DQA1 protein; Exons; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Glomerulonephritis, Membranous - diagnosis; Glomerulonephritis, Membranous - ethnology; Glomerulonephritis, Membranous - genetics; Glomerulonephritis, Membranous - immunology; Histocompatibility antigen HLA; HLA-DQ alpha-Chains - genetics; HLA-DQ alpha-Chains - immunology; Humans; Japan; Leukocytes (mononuclear); Male; Medicine; Medicine & Public Health; Membranous nephropathy; Middle Aged; Nephrology; Nephropathy; Nucleotide sequence; Original Article; Phenotype; Polymorphism; Polymorphism, Single Nucleotide; Receptors, Phospholipase A2 - genetics; Risk Factors; Single-nucleotide polymorphism; Urology; Japanese cohort; Single nucleotide polymorphism; Bucillamine; Membranous nephropathy; M-type phospholipase A2 receptor
• ISSN: 1342-1751; 1437-7799
• DOI: 10.1007/s10157-017-1471-0

Background
Several recent studies in patients with idiopathic membranous nephropathy (iMN) from Western and Asian counties showed that some single nucleotide polymorphisms (SNPs) within the
PLA2R1
and
HLA
-
DQA1
genes are significantly associated with iMN. However, there is only 1 report on analysis of
PLA2R1
and
HLA
regions in Japanese patients with iMN.
Methods
A total of 58 patients with iMN, 26 patients with secondary MN (sMN), and 50 patients with other diseases were enrolled. All patients were Japanese. We selected 6 SNPs within
PLA2R1
and 1 SNP within
HLA
-
DQA1
, which were significantly associated with iMN in reported white European cohorts, and sequenced these exons using genomic DNA prepared from peripheral mononuclear cells from each patient. We then analyzed differences in
PLA2R1
and
HLA
-
DQA1
sequence variants among the 3 groups.
Results
Genotypic and allelic frequency distributions for 3 out of 6 SNPs within
PLA2R1
, rs3749117, rs35771982, and rs2715918 were significantly different between the iMN and control groups. Allelic frequency distributions for SNP rs2187668 within
HLA
-
DQA1
were significantly different between the iMN and control groups. There were no correlations between
PLA2R1
and
HLA
-
DQA1
sequence variants and clinical parameters in patients with iMN. There were no significant differences in genotypic or allelic frequency distributions for examined SNPs between the sMN and control groups.
Conclusions
There are some differences in
PLA2R1
SNP distributions between previously reported cohorts from other countries and our Japanese cohort of patients with iMN, while there is a significant association between SNP rs35771982 and iMN in most of reported cohorts.