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

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.

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The linkage disequilibrium (LD) structures of PARL (a) and PINK1 (b) in leprosy patients and healthy controls from the Yuxi Prefecture and pooled control samples. Black squares represented high LD as measured by r2, gradually coloring down to white squares of low LD. The individual square showed the r2 value for each SNP pair (r2 value is multiplied by 100). The pooled control samples contained the reported Han Chinese without leprosy from Hunan Province (N = 984), Shanghai (N = 1526)27, and the Yuxi control samples in this study (Yuxi).
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f1: The linkage disequilibrium (LD) structures of PARL (a) and PINK1 (b) in leprosy patients and healthy controls from the Yuxi Prefecture and pooled control samples. Black squares represented high LD as measured by r2, gradually coloring down to white squares of low LD. The individual square showed the r2 value for each SNP pair (r2 value is multiplied by 100). The pooled control samples contained the reported Han Chinese without leprosy from Hunan Province (N = 984), Shanghai (N = 1526)27, and the Yuxi control samples in this study (Yuxi).

Mentions: The minor allele frequencies (MAF) of the SNPs analyzed in this study ranged from 5.8% to 48.4% (Table 1). The power to detect an odds ratio (OR) value as 1.6 for risk allele was expected to be above 77.0% (Fig. S1). SNPs rs10937153, rs1573132 and rs607254 were not in Hardy-Weinberg equilibrium in controls (Table S1, P < 0.05) and were excluded in the following analyses. The allele and genotype frequencies of the 10 SNPs in 527 leprosy patients, 583 healthy subjects from the Yuxi Prefecture, Yunnan Province, and pooled 3093 leprosy-unaffected controls were listed in Tables 1 and 2. We constructed the linkage disequilibrium (LD) map of all the tested SNPs in the Yuxi leprosy cases, Yuxi controls and pooled leprosy-unaffected controls (Fig. 1), and observed similar LD structures for these populations. We further performed the principal component (PC) analysis for the studied populations based on the observed genotype frequencies of the 10 SNPs, together with data of the CHB, CHD, JPT, CEU populations from the HapMap data set35. The Yuxi leprosy patient, Yuxi controls and the reported controls from Hunan Province and Shanghai were clustered together, suggesting no substantial population substructure between the cases and controls (Fig. S2).


Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China
The linkage disequilibrium (LD) structures of PARL (a) and PINK1 (b) in leprosy patients and healthy controls from the Yuxi Prefecture and pooled control samples. Black squares represented high LD as measured by r2, gradually coloring down to white squares of low LD. The individual square showed the r2 value for each SNP pair (r2 value is multiplied by 100). The pooled control samples contained the reported Han Chinese without leprosy from Hunan Province (N = 984), Shanghai (N = 1526)27, and the Yuxi control samples in this study (Yuxi).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: The linkage disequilibrium (LD) structures of PARL (a) and PINK1 (b) in leprosy patients and healthy controls from the Yuxi Prefecture and pooled control samples. Black squares represented high LD as measured by r2, gradually coloring down to white squares of low LD. The individual square showed the r2 value for each SNP pair (r2 value is multiplied by 100). The pooled control samples contained the reported Han Chinese without leprosy from Hunan Province (N = 984), Shanghai (N = 1526)27, and the Yuxi control samples in this study (Yuxi).
Mentions: The minor allele frequencies (MAF) of the SNPs analyzed in this study ranged from 5.8% to 48.4% (Table 1). The power to detect an odds ratio (OR) value as 1.6 for risk allele was expected to be above 77.0% (Fig. S1). SNPs rs10937153, rs1573132 and rs607254 were not in Hardy-Weinberg equilibrium in controls (Table S1, P < 0.05) and were excluded in the following analyses. The allele and genotype frequencies of the 10 SNPs in 527 leprosy patients, 583 healthy subjects from the Yuxi Prefecture, Yunnan Province, and pooled 3093 leprosy-unaffected controls were listed in Tables 1 and 2. We constructed the linkage disequilibrium (LD) map of all the tested SNPs in the Yuxi leprosy cases, Yuxi controls and pooled leprosy-unaffected controls (Fig. 1), and observed similar LD structures for these populations. We further performed the principal component (PC) analysis for the studied populations based on the observed genotype frequencies of the 10 SNPs, together with data of the CHB, CHD, JPT, CEU populations from the HapMap data set35. The Yuxi leprosy patient, Yuxi controls and the reported controls from Hunan Province and Shanghai were clustered together, suggesting no substantial population substructure between the cases and controls (Fig. S2).

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.


Related in: MedlinePlus