Distributions of susceptibility loci of Parkinson's disease and multiple sclerosis on human chromosomes.

Dear Editor,

It has been suggested that genes are distributed non-randomly on human chromosomes (Hecht, 1988[4]; Lima-de-Faria and Mitelman, 1988[8]; Lima-de-Faria et al., 1991[9]; Mouchiroud et al., 1991[10]; Saccone et al., 1992[15]; 1996[14]; Musio et al., 2002[11]; Rafiee et al., 2008[12]). Recently we reported that polymorphic loci associated with susceptibility to either breast cancer (Saify and Saadat, 2012[16]) or schizophrenia (Saadat, 2013[13]) are non-randomly distributed on some human chromosome segments.

It is well established that Parkinson's disease (PD) is a complex multifactorial neurodegenerative disease that was considered the result of environmental and genetic factors (Siderowf, 2001[17]; Warner and Schapira, 2003[20]; Allam et al., 2005[1]; Trinh and Farrer, 2013[19]). Based on familial aggregation studies and the study of twins, it has been established that genetic elements have significant roles in the development of multiple sclerosis (MS) (Ascherio, 2013[2]; Cree, 2014[3]).

Several meta-analyses based on genetic polymorphisms have been widely performed to assess the association between particular gene variants and PD or MS risk. Some of these studies were indicating that the study polymorphisms were not associated with the risks of PD or MS. However, in other studies significant associations with risks of PD or MS, at least in a specific ethnic group were reported (Lill et al., 2012[7];[6]). Taken together, we suggested that loci associated with the risk of PD or MS may be distributed non-randomly on human chromosomes. Therefore the present study was carried out.

Meta-analysis studies published up to February 2014 with information of genetic polymorphisms and PD risk were identified using Parkinson's Disease Research Forum (PDGene database http://www.pdgene.org) electronic database (Lill et al., 2012[7]). Information of genetic polymorphisms and MS risk was identified using MSGene database (http://www.msgene.org) electronic database (Lill et al., 2012[6]).

To evaluate the non-randomness distribution of susceptible loci on each chromosomal band(s) the method of Tai et al. (1993[18]) was used. The relative width of each band was measured using the diagram of the International System for Chromosome Nomenclature (ISCN, 1981[5]). A probability of P<0.05 was considered statistically significant.

There were 881 studies concerning the associations between 915 genes (3446 polymorphisms) and risk of PD. Table 1(Tab. 1) shows the genes with their genetic polymorphisms associated with susceptibility to PD in at least one ethnic group. There are 20 loci associated with risk of PD. Statistical analysis revealed that the PD susceptible loci distributed non-randomly on human chromosomes. Human chromosome segments 1q31-1q32 (P<0.001) and 17q21-q23 (P<0.001) were bearing significantly higher numbers of susceptible loci for PD. There are four genes which associated with susceptibility to PD on 1q31-q32 (SLC45A3, NUCKS1, SLC41A1, and PM20D1/ PARK16). There are three genes which associated with susceptibility to PD on 17q21-q23 (PLEKHM1, MAPT, and MED13).

Table 1

List of genes that associated with Parkinson's disease risk

There were 789 studies concerning the associations between 809 genes (2907 polymorphisms) and susceptibility to MS. Table 2(Tab. 2) shows the genes with their genetic polymorphisms associated with risk of MS in at least one ethnic group. There are 44 loci associated with MS risk. Statistical analysis revealed that the MS susceptible loci distributed non-randomly on human chromosomes. Human chromosome segments 1p22, 5p13, 17q12-21.2, 19p13, and 19q13 (P<0.001) were bearing significantly higher numbers of susceptible loci for MS. There are four genes which associated with MS risk on 5p13 (IL7R, PTGER4, C7, and HEATR7B2). There are three genes which associated with susceptibility to MS on each chromosomal segments of 1p22 (EVI5, RPL5, and FAM69A), 17q12-21.2 (CCL8, CCL1, and STAT), 19p13 (VAV1, TYK2, and IFI30) and 19q13 (TGFB1, APOE, and LILRA3).

Table 2

List of genes that associated with multiple sclerosis risk

Already the non-random distributions of polymorphic loci associated with both breast cancer (Saify and Saadat, 2012[16]) and schizophrenia (Saadat, 2013[13]), were reported. A mass screening test might be designed using genes located on above mentioned chromosome segments for diagnosis of PD and MS. It is suggested that using simultaneously polymorphisms of the genes located on the above mentioned chromosome segment can increase the sensitivity and specificity of the mass screening test for detecting high risk individuals for developing Parkinson's disease and multiple sclerosis.

Acknowledgements

This study was supported by Shiraz University.

Conflict of interest

No conflicts of interest exist.