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

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.

A pleiotropic effect of theAPOEgene: association ofAPOEpolymorphisms with multibacillary leprosy in Han Chinese from Southwest China

“…Two nonsynonymous SNPs [rs429358 (p.C130R) and rs7412 (p.R176C)] that were associated with AD were also included in the analysis. SNPs rs405509, rs769450 and rs439401 were genotyped using the SNaPshot assay (Thermo Fisher Scientific, Waltham, MA, U.S.A.) following the procedure described in our previous studies, whereas rs429358 and rs7412 were genotyped by direct sequencing using the ABI 3730xl DNA Analyzer (Thermo Fisher Scientific). The primers used for genotyping are shown in Table S1 (see Supporting Information).…”

“…The exons and flanking regions of APOE were captured using the NimbleGene SeqCap EZ Human Exome v3.0 (Roche, Pleasanton, CA, U.S.A.) and sequenced by the Illumina HiSeq 4000 Genome Analyzer (Illumina, San Diego, CA, U.S.A.). The alignment and variant calling for the APOE exons was performed using the same procedure described in our previous study …”

“…A previously published genome‐wide association study (GWAS) in Han Chinese populations has reported many leprosy susceptibility genes CCDC122 , LACC1 , NOD2 , TNFSF15 , HLA‐DR , RIPK2 and LRRK2 . In addition, more than 60 susceptibility genes were identified using a candidate gene approach, such as NOD2 , VDR , MBL, TNF , MRC1 , IFNG , MBL2 , TLR1 , TOLLIP , PINK1 and PARL …”

Advances in the Immunology and Genetics of Leprosy

“…Leprosyassociated class I HLA genes include HLA-A * 28 in Mestizo populations (121) and HLA-B * 15 and HLA-C * 05 in the Brazilian population (122). Leprosy-associated class II HLA genes include HLA-DQA1 in Brazilians (123), HLA-DQB1 * 06 and HLA-DQB1 * 07 in Mestizo populations (121), HLA-DRB1 * 11 in Brazilians (124), HLA-DRB1 * 1501 in Chinese and Indians (125,126), and HLA-DRB1 * 1501 in Indians (125,126). In addition, other antigen-processing and presentation-related genes were found to be associated with leprosy, such as the MICA gene (127), MICB gene (127), HLA-G gene (128), and TAP1 gene (129).…”

Polymorphisms in the TGFB1 and IL2RA genes are associated with clinical forms of leprosy in Brazilian population

“… 17 Besides, several studies have produced replicated association data for clinical forms of leprosy in the Chinese population. 13 , 14 , 18 , 19 , 20 , 21 , 22 , 23 From linkage scans in two studies, one peak at chromosomal region 10p13 for PB leprosy was discovered. 24 , 25 …”