Genomics and disease progression in IgA nephritis.
Apart from clinical, histological and biochemical indices, genomics are now being employed to unravel the pathogenetic mechanisms in the disease progression of IgA nephritis (IgAN). The results of angiotensin converting enzyme (ACE) gene polymorphism have been controversial. Those patients with the DD genotype seem to have a poorer prognosis. However, with high dose angiotensin receptor blocker (ARB) therapy, the ACE gene polymorphism status of a patient may no longer be a matter for concern as those with the DD genotype would also respond favourably to high dose ARB therapy. Association studies with gene sequencing and haplotypes have suggested that multiple genes are involved in the pathogenesis of IgAN. Some workers have reported a synergistic effect in the combined analysis of AGT-M235T and ACE I/D polymorphism. With the use of deoxyribo nucleic acid (DNA) microarray, tens of thousands of gene expressions genome-wide can be examined together simultaneously. A locus of familial IgAN has been described with strong evidence of linkage to IgAN1 on chromosome 6q22-23. Two other loci were reported at 4q26-31 and 17q12-22. DNA microarray techniques could also help in the identification of specific pathogenic genes that are up- or down-regulated and this may allow genome wide analyses of these genes and their role in the pathogenesis and progression of IgAN. Recently, using genome-wide association studies (GWAS) more loci for disease susceptibility for IgAN have been identified at 17p13, 8p23, 22q12, 1q32 and 6p21.
Department of Renal Medicine, Singapore General Hospital, Singapore.
Keng Thye
KT
Woo
Yeow Kok
YK
Lau
Hui Lin
HL
Choong
Han Khim
HK
Tan
Marjorie Wy
MW
Foo
Evan Jc
EJ
Lee
Vathsala
V
Anantharaman
Grace Sl
GS
Lee
Hui Kim
HK
Yap
Zhao
Z
Yi
Stephanie
S
Fook-Chong
Kok Seng
KS
Wong
Choong Meng
CM
Chan
D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D023281:Genomics / Q000379:methods; D005922:Glomerulonephritis, IGA / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide
D057911:Angiotensin Receptor Antagonists