**2. Variability among individuals: why it is important to study gene polymorphisms**

Gene polymorphisms are the most common type of genetic variations in humans. They are present in the human population at frequency higher than 1% and differ from DNA mutations which are generally observed at extremely low frequency and in a restricted number of individuals. While gene polymorphisms are not necessarily associated to a specific disease, the gene mutation is generally known to cause a genetic disease. In humans the simplest type of polymorphism is the single nucleotide polymorphisms (SNPs), representing the most common type of nucleotide variation where a single base is substituted by another one (**Figure 1**). A SNP in the coding region of a gene may have four different effects on the resulting protein: (1) *synonymous substitution*, also known as silent mutation, causing no amino acid change in the protein, (2) *non-synonymous substitution* where a nucleotide mutation alters the amino acid sequence of a protein, (3) *missense substitution* consisting of an amino acid change with another and (4) *nonsense substitution* resulting in end of protein translation by a termination codon. About half of all the coding sequences of SNPs end up in non-synonymous codon changes. However SNPs may occur also in the regulatory region of the gene, affecting various properties of the protein. These SNPs may influence the protein in terms of quantity and quality, activity, processing and trafficking [2]. In the last 20 years, SNPs have raised a lot of

**67**

*The Role of Genetic Polymorphisms in the Occupational Exposure*

interest in many scientific fields related to public health and disease. They are also investigated in many scientific research areas, ranging from the human ethnicity study to the genetics of populations, personalized medicine, pathology, epidemiology, pharmacology, immunology and nutrition. More recently they have been considered relevant also for their role in the exposure science, a novel scientific branch linked to toxicology which characterizes and elucidates the contact of humans with dangerous chemical, physical and biological agents which represent a potential risk for the human health [3]. Actually the environmental exposure, in which also the occupational exposure is comprised, is acknowledged to play an important role in common chronic diseases, representing a major health concern in the economically developed countries. In this context the study of SNPs has a fundamental role to detect the human response to toxic and dangerous substances. Although the majority of SNPs of the human genome are of low prevalence [4], including the genes implicated in metabolism of environmental chemicals, these may substantially contribute to increase the population disease burden [5]. Since the exposure factors are numerous and several chronic diseases remain uncertain, it is fundamental to study the human genetic variation to understand the exposure-disease associations within the global population [6]. On the whole the genetic diversity associated to the variability of polymorphisms and to the genetic recombination is a valuable resource for humans and other living organisms. The interactions between the genetics of human beings and the surrounding environment reciprocally shape one with each other in order to reach an equilibrium. However such equilibrium might be perturbed by several exogenous factors such as the influence of natural selection, the global climate change, the re-emergence of extinct diseases and the admixing of different ethnicities due to massive migrations from one country to another. All these factors may contribute to change the variation of the gene polymorphism pool in the worldwide population. Nowadays the characterization of gene polymorphisms of the human population is carried out on individuals belonging to the same ethnicity so as to identify ethnic-specific gene/allele frequencies. This strategy should help geneticists to identify the genotype frequencies typical of members of a community sharing the same language, culture, religion, tradition, nationality, ancestry, nutrition, habits and lifestyle which influence the genetic background of the group [7]. For this reason the investigational studies of polymorphic genes refer more to the concept of ethnicity than to the race. The genetic characterization of separate ethnic groups provides useful information to evaluate the difference in the susceptibility risk of each cluster. Several papers have been published to report the typical genotype frequency of different gene polymorphisms in selected ethnicities [8–11]. However, due to the abundance of variation in gene polymorphisms, the characterization of the gene pool of a specific group of individuals is incomplete, and the genotype frequencies are known only for polymorphisms which have been investigated for their role or association to a specific susceptibility or disease. To our knowledge the commonest public databases collecting the gene polymorphisms available to the scientific community are the following: (1) the single nucleotide polymorphism database (dbSNP), a public archive for genetic variation hosted by the National Center for Biotechnology Information (NCBI) (https://www.ncbi.nlm. nih.gov/snp), and (2) the Ensembl project of genome databases for vertebrates and other eukaryotic species (http://grch37.ensembl.org/Homo\_sapiens/Variation), which is the one we are using in the study of the human SNPs. These two archives represent a fundamental resource for our investigational studies on human genetic diversity when the laboratory genotyping is not feasible. In this chapter we describe some of our studies carried out during the biomonitoring campaigns of exposed workers where the biomarkers of dose, effect and susceptibility have been assessed in the occupational exposure. In addition we show also a statistical model we

*DOI: http://dx.doi.org/10.5772/intechopen.86975*

**Figure 1.** *Variation of single nucleotide in the human DNA coding sequence among individuals.*

## *The Role of Genetic Polymorphisms in the Occupational Exposure DOI: http://dx.doi.org/10.5772/intechopen.86975*

*The Recent Topics in Genetic Polymorphisms*

**polymorphisms**

increase further the genetic variation in the population.

of the surrounding environment on our genotype and on our physiological, physical and behavioral habits. Such influence, namely, epigenetics, means that the heritable changes in gene expression are not due to alteration in the DNA sequence but to some modifications occurring upon the DNA without changing the genetic code. That said, although we are aware the genetic variability is something peculiar to every human being, regardless of the inheritance of favorable or unfavorable genes, the transmission to the offspring will be modulated by epigenetics contributing to

**2. Variability among individuals: why it is important to study gene** 

Gene polymorphisms are the most common type of genetic variations in humans. They are present in the human population at frequency higher than 1% and differ from DNA mutations which are generally observed at extremely low frequency and in a restricted number of individuals. While gene polymorphisms are not necessarily associated to a specific disease, the gene mutation is generally known to cause a genetic disease. In humans the simplest type of polymorphism is the single nucleotide polymorphisms (SNPs), representing the most common type of nucleotide variation where a single base is substituted by another one (**Figure 1**). A SNP in the coding region of a gene may have four different effects on the resulting protein: (1) *synonymous substitution*, also known as silent mutation, causing no amino acid change in the protein, (2) *non-synonymous substitution* where a nucleotide mutation alters the amino acid sequence of a protein, (3) *missense substitution* consisting of an amino acid change with another and (4) *nonsense substitution* resulting in end of protein translation by a termination codon. About half of all the coding sequences of SNPs end up in non-synonymous codon changes. However SNPs may occur also in the regulatory region of the gene, affecting various properties of the protein. These SNPs may influence the protein in terms of quantity and quality, activity, processing and trafficking [2]. In the last 20 years, SNPs have raised a lot of

**66**

**Figure 1.**

*Variation of single nucleotide in the human DNA coding sequence among individuals.*

interest in many scientific fields related to public health and disease. They are also investigated in many scientific research areas, ranging from the human ethnicity study to the genetics of populations, personalized medicine, pathology, epidemiology, pharmacology, immunology and nutrition. More recently they have been considered relevant also for their role in the exposure science, a novel scientific branch linked to toxicology which characterizes and elucidates the contact of humans with dangerous chemical, physical and biological agents which represent a potential risk for the human health [3]. Actually the environmental exposure, in which also the occupational exposure is comprised, is acknowledged to play an important role in common chronic diseases, representing a major health concern in the economically developed countries. In this context the study of SNPs has a fundamental role to detect the human response to toxic and dangerous substances. Although the majority of SNPs of the human genome are of low prevalence [4], including the genes implicated in metabolism of environmental chemicals, these may substantially contribute to increase the population disease burden [5]. Since the exposure factors are numerous and several chronic diseases remain uncertain, it is fundamental to study the human genetic variation to understand the exposure-disease associations within the global population [6]. On the whole the genetic diversity associated to the variability of polymorphisms and to the genetic recombination is a valuable resource for humans and other living organisms. The interactions between the genetics of human beings and the surrounding environment reciprocally shape one with each other in order to reach an equilibrium. However such equilibrium might be perturbed by several exogenous factors such as the influence of natural selection, the global climate change, the re-emergence of extinct diseases and the admixing of different ethnicities due to massive migrations from one country to another. All these factors may contribute to change the variation of the gene polymorphism pool in the worldwide population. Nowadays the characterization of gene polymorphisms of the human population is carried out on individuals belonging to the same ethnicity so as to identify ethnic-specific gene/allele frequencies. This strategy should help geneticists to identify the genotype frequencies typical of members of a community sharing the same language, culture, religion, tradition, nationality, ancestry, nutrition, habits and lifestyle which influence the genetic background of the group [7]. For this reason the investigational studies of polymorphic genes refer more to the concept of ethnicity than to the race. The genetic characterization of separate ethnic groups provides useful information to evaluate the difference in the susceptibility risk of each cluster. Several papers have been published to report the typical genotype frequency of different gene polymorphisms in selected ethnicities [8–11]. However, due to the abundance of variation in gene polymorphisms, the characterization of the gene pool of a specific group of individuals is incomplete, and the genotype frequencies are known only for polymorphisms which have been investigated for their role or association to a specific susceptibility or disease. To our knowledge the commonest public databases collecting the gene polymorphisms available to the scientific community are the following: (1) the single nucleotide polymorphism database (dbSNP), a public archive for genetic variation hosted by the National Center for Biotechnology Information (NCBI) (https://www.ncbi.nlm. nih.gov/snp), and (2) the Ensembl project of genome databases for vertebrates and other eukaryotic species (http://grch37.ensembl.org/Homo\_sapiens/Variation), which is the one we are using in the study of the human SNPs. These two archives represent a fundamental resource for our investigational studies on human genetic diversity when the laboratory genotyping is not feasible. In this chapter we describe some of our studies carried out during the biomonitoring campaigns of exposed workers where the biomarkers of dose, effect and susceptibility have been assessed in the occupational exposure. In addition we show also a statistical model we

previously elaborated to identify ethnic-specific differences in the susceptibility risk to the typical exposure found in the workplace. In such model a statistical analysis has been done using the publicly available genotype frequency of four ethnic groups (Africans, East Asians, South Asians and Europeans) downloaded from the Ensembl project of genome databases.
