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Advances in lupus genetics and epigenetics
#MMPMID25010439
Deng Y
; Tsao BP
Curr Opin Rheumatol
2014[Sep]; 26
(5
): 482-92
PMID25010439
show ga
PURPOSE OF REVIEW: Genome-wide association studies have identified more than 50
robust loci associated with systemic lupus erythematosus (SLE) susceptibility,
and follow-up studies help reveal candidate causative genetic variants and their
biological relevance contributing to the development of SLE. Epigenetic
modulation is emerging as an important mechanism for understanding how the
implicated genes interact with environmental factors. We review recent progress
toward identifying causative variants of SLE-associated loci and epigenetic
impact on lupus, especially genetic-epigenetic interactions that modulate
expression levels of SLE susceptibility genes. RECENT FINDINGS: A few SLE-risk
loci have been refined to localize likely causative variants responsible for the
observed genome-wide association study signals. Few of such variants disrupt
coding sequences resulting in gain or loss of function for the encoded protein,
whereas most fall in noncoding regions with potential to regulate gene expression
through alterations in transcriptional activity, splicing, mRNA stability and
epigenetic modifications. Multiple key pathways related to the SLE pathogenesis
have been indicated by the identified genetic risk factors, including type I
interferon signaling pathway that can also be regulated by epigenetic changes
occurred in SLE. SUMMARY: These findings provide novel insights into the disease
pathogenesis and promise better diagnostic accuracy and new therapeutic targets
for patient management.
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