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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.


eQTL analysis of the PARL and PINK1 genes.cis and trans eQTL of the PARL and PINK1 tag SNPs in human blood, skin and nerve tissues were identified by using the GTEx (http://www.gtexportal.org/home)38 and HaploReg dataset (http://www.broadinstitute.org/mammals/haploreg/haploreg.php)54.
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f2: eQTL analysis of the PARL and PINK1 genes.cis and trans eQTL of the PARL and PINK1 tag SNPs in human blood, skin and nerve tissues were identified by using the GTEx (http://www.gtexportal.org/home)38 and HaploReg dataset (http://www.broadinstitute.org/mammals/haploreg/haploreg.php)54.

Mentions: We tested the expression quantitative trait loci (eQTLs) of 34 SNPs (including 5 index tag SNPs and 21 captured PARL SNPs from the HapMap database35, and 8 tag SNPs in PINK1) in leprosy-related human blood, skin and nerve tissues from the Genotype-Tissue Expression project (GTEx, http:// www.gtexportal.org/ home/38). We found that 18 of 26 PARL SNPs were significant cis eQTLs in whole blood (P < 1.0 × 10−4). Among them, 10 of 26 SNPs were remarkably significant (P < 1.0 × 10−8). Notably, SNP rs7644746 that was tagged by the risk SNP rs7653061 reached a P value of 5.6 × 10−24 in blood (Fig. 2a). PINK1 SNP rs10916840 was a cis eQTL in skin tissue (1.5 × 10−9) based on the GTEx dataset38, whereas rs4704 was a significant trans eQTL in whole blood (3.1 × 10−30; Fig. 2b). Both SNPs affected the PINK1 mRNA expression level.


Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China
eQTL analysis of the PARL and PINK1 genes.cis and trans eQTL of the PARL and PINK1 tag SNPs in human blood, skin and nerve tissues were identified by using the GTEx (http://www.gtexportal.org/home)38 and HaploReg dataset (http://www.broadinstitute.org/mammals/haploreg/haploreg.php)54.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: eQTL analysis of the PARL and PINK1 genes.cis and trans eQTL of the PARL and PINK1 tag SNPs in human blood, skin and nerve tissues were identified by using the GTEx (http://www.gtexportal.org/home)38 and HaploReg dataset (http://www.broadinstitute.org/mammals/haploreg/haploreg.php)54.
Mentions: We tested the expression quantitative trait loci (eQTLs) of 34 SNPs (including 5 index tag SNPs and 21 captured PARL SNPs from the HapMap database35, and 8 tag SNPs in PINK1) in leprosy-related human blood, skin and nerve tissues from the Genotype-Tissue Expression project (GTEx, http:// www.gtexportal.org/ home/38). We found that 18 of 26 PARL SNPs were significant cis eQTLs in whole blood (P < 1.0 × 10−4). Among them, 10 of 26 SNPs were remarkably significant (P < 1.0 × 10−8). Notably, SNP rs7644746 that was tagged by the risk SNP rs7653061 reached a P value of 5.6 × 10−24 in blood (Fig. 2a). PINK1 SNP rs10916840 was a cis eQTL in skin tissue (1.5 × 10−9) based on the GTEx dataset38, whereas rs4704 was a significant trans eQTL in whole blood (3.1 × 10−30; Fig. 2b). Both SNPs affected the PINK1 mRNA expression level.

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&thinsp;=&thinsp;0.019) and multibacillary leprosy (MB, Padjusted&thinsp;=&thinsp;0.020) at the allelic level. rs12631031 and rs7653061 in PARL were associated with leprosy and MB (dominant model, Padjusted&thinsp;&lt;&thinsp;0.05) at the genotypic level. PINK1 SNP rs4704 was associated with leprosy at the genotypic level (Padjusted&thinsp;=&thinsp;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.