Paraoxonase 1 Q192R and L55M polymorphisms and susceptibility to amyotrophic lateral sclerosis: a meta-analysis

Abstract

This study aimed to investigate whether paraoxonase 1 (PON1) Q192R and L55M polymorphisms are associated with susceptibility to amyotrophic lateral sclerosis (ALS). We conducted a meta-analysis of the associations between the PON1 Q192R and L55M polymorphisms and ALS. A total of 2,831 patients and 3,123 controls from eight studies of the PON1 Q192R polymorphism and seven studies of the PON1 L55M T polymorphism were considered for this study. Meta-analysis showed no association between ALS and the PON1 192R allele (OR = 1.052, 95 % CI = 0.923-1.207, p = 0.447), and the PON1 55M allele (OR = 1.015, 95 % CI = 0.884-1.164, p = 0.837) in all study subjects. Similarly, no association was found between ALS and the PON1 Q192R and L55M polymorphisms using recessive, dominant or homozygote contrast models. Stratification by ethnicity indicated no association between ALS and the PON1 192R allele (OR = 1.058, 95 % CI = 0.910-1.231, p = 0.464) and the PON1 55M allele (OR = 1.027, 95 % CI = 0.889-1.185, p = 0.721) in the European population. This meta-analysis showed lack of associations between PON1 Q192R and L55M polymorphisms and susceptibility to ALS in the European population.

Genetic polymorphisms in amyotrophic lateral sclerosis: Evidence for implication in detoxification pathways of environmental toxicants

“…Furthermore, two meta-analyses have revealed negative results (Lee et al, 2015;Wills et al, 2009). (Lee et al, 2015). In view of the previous results, the role of PON1 gene in sALS remains uncertain.…”

“…A recent meta-analysis also provides strong evidence that the PON1 rs705379 is associated with the risk of AD (Nie et al, 2017). However, the results of case-control studies and metaanalyses remain conflicting (Lee et al, 2015;Liu et al, 2012;Menini and Gugliucci, 2014;Pi et al, 2012;Wills et al, 2009;Zintzaras and Hadjigeorgiou, 2004). L55M and Q192R variants have been found to increase the risk of organophosphate toxicity in a population-dependent manner (You et al, 2013).…”

“…SNPs across PON1 failed to show evidence about in North American, French, Canadian, Swedish, English, Italian, Chinese, Polish, Dutch, British, German cohorts (Chen et al, 2012a;Kasperaviciute et al, 2007;Ricci et al, 2011;Saeed et al, 2006;Valdmanis et al, 2008;van Blitterswijk et al, 2012;Zawislak et al, 2010). Furthermore, two meta-analyses have revealed negative results (Lee et al, 2015;Wills et al, 2009). (Lee et al, 2015).…”

The paraoxonase disruption hypothesis in sporadic ALS steamrolled

“…Dear Editor, I have read with interest a recent report by Lee and coworkers on the putative role of PON1 variants in sporadic amyotrophic lateral sclerosis (ALS) [1]. In their report, the authors refute an association of two missense substitutions on the phenotype under study based on data from eight earlier case-control studies.…”

“…Thus for Q192R, they have exchanged ''QQ'' for ''RR'' genotypes and for L55M, they have confused ''LL'' with ''MM'' genotypes [7]. Genotypes listed in Table 2 [1] are either in error [7][8][9][10] or missing [3]. The listing of ''allele counts'' in lieu of genotypes in Table 2 [1] is erratic and both p values and sample sizes contain substantial errors (e.g.…”