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Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China

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ABSTRACT

Leprosy is a chronic infectious and neurological disease caused by Mycobacterium leprae, an unculturable pathogen with massive genomic decay and dependence on host metabolism. We hypothesized that mitochondrial genes PARL and PINK1 would confer risk to leprosy. Thirteen tag SNPs of PARL and PINK1 were analyzed in 3620 individuals with or without leprosy from China. We also sequenced the entire exons of PARL, PINK1 and PARK2 in 80 patients with a family history of leprosy by using the next generation sequencing technology (NGS). We found that PARL SNP rs12631031 conferred a risk to leprosy (Padjusted = 0.019) and multibacillary leprosy (MB, Padjusted = 0.020) at the allelic level. rs12631031 and rs7653061 in PARL were associated with leprosy and MB (dominant model, Padjusted < 0.05) at the genotypic level. PINK1 SNP rs4704 was associated with leprosy at the genotypic level (Padjusted = 0.004). We confirmed that common variants in PARL and PINK1 were associated with leprosy in patients underwent NGS. Furthermore, PARL and PINK1 could physically interact with each other and were involved in the highly connected network formed by reported leprosy susceptibility genes. Together, our results showed that PARL and PINK1 genetic variants are associated with leprosy.

No MeSH data available.


Protein interaction network of the PARL and PINK1 genes.PARL can directly interact with PINK1 according to the GeneMANIA database (http://genemania.org/)41. The minimum required interaction score is >0.7 and the line thickness indicates the strength of data support.
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f3: Protein interaction network of the PARL and PINK1 genes.PARL can directly interact with PINK1 according to the GeneMANIA database (http://genemania.org/)41. The minimum required interaction score is >0.7 and the line thickness indicates the strength of data support.

Mentions: To evaluate the protein interaction with PARL and PINK1, we used the GeneMANIA prediction server41 and identified that PARL could physically interacted and co-expressed with PINK1. PARL and PINK1 could directly or indirectly interact with many proteins, such as FXR1, NDUFB5, TRAP1 and PARK2 (Fig. 3). Note that PINK1 directly interacted with PARK2, which was identified as a leprosy risk gene in several populations424344. However, our NGS analysis for the PARK2 gene revealed no association of this gene with leprosy though we observed positive associations between PARL and leprosy or between PINK1 and leprosy in this relatively small sample. This observation was consistent with a previous report for no association of PARK2 SNPs with leprosy in Han Chinese population45. However, it should be noted that our exon sequencing of the PARK2 gene did not cover its promoter region, and we could not exclude a possibility that there existed leprosy-associated SNP(s).


Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China
Protein interaction network of the PARL and PINK1 genes.PARL can directly interact with PINK1 according to the GeneMANIA database (http://genemania.org/)41. The minimum required interaction score is >0.7 and the line thickness indicates the strength of data support.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120299&req=5

f3: Protein interaction network of the PARL and PINK1 genes.PARL can directly interact with PINK1 according to the GeneMANIA database (http://genemania.org/)41. The minimum required interaction score is >0.7 and the line thickness indicates the strength of data support.
Mentions: To evaluate the protein interaction with PARL and PINK1, we used the GeneMANIA prediction server41 and identified that PARL could physically interacted and co-expressed with PINK1. PARL and PINK1 could directly or indirectly interact with many proteins, such as FXR1, NDUFB5, TRAP1 and PARK2 (Fig. 3). Note that PINK1 directly interacted with PARK2, which was identified as a leprosy risk gene in several populations424344. However, our NGS analysis for the PARK2 gene revealed no association of this gene with leprosy though we observed positive associations between PARL and leprosy or between PINK1 and leprosy in this relatively small sample. This observation was consistent with a previous report for no association of PARK2 SNPs with leprosy in Han Chinese population45. However, it should be noted that our exon sequencing of the PARK2 gene did not cover its promoter region, and we could not exclude a possibility that there existed leprosy-associated SNP(s).

View Article: PubMed Central - PubMed

ABSTRACT

Leprosy is a chronic infectious and neurological disease caused by Mycobacterium leprae, an unculturable pathogen with massive genomic decay and dependence on host metabolism. We hypothesized that mitochondrial genes PARL and PINK1 would confer risk to leprosy. Thirteen tag SNPs of PARL and PINK1 were analyzed in 3620 individuals with or without leprosy from China. We also sequenced the entire exons of PARL, PINK1 and PARK2 in 80 patients with a family history of leprosy by using the next generation sequencing technology (NGS). We found that PARL SNP rs12631031 conferred a risk to leprosy (Padjusted = 0.019) and multibacillary leprosy (MB, Padjusted = 0.020) at the allelic level. rs12631031 and rs7653061 in PARL were associated with leprosy and MB (dominant model, Padjusted < 0.05) at the genotypic level. PINK1 SNP rs4704 was associated with leprosy at the genotypic level (Padjusted = 0.004). We confirmed that common variants in PARL and PINK1 were associated with leprosy in patients underwent NGS. Furthermore, PARL and PINK1 could physically interact with each other and were involved in the highly connected network formed by reported leprosy susceptibility genes. Together, our results showed that PARL and PINK1 genetic variants are associated with leprosy.

No MeSH data available.