The Role of Genetic Polymorphisms in the Occupational Exposure

The results of recent studies indicate the potential role of gamma-aminobutyric acid (GABA), as an inhibitory mediator of the central nervous system, in the pathogenesis of obstructive sleep apnea syndrome (OSAS) ‒ a common disorder that often accompanies asthma. The aim of the study was to investigate the possible role of some GABAergic system genetic polymorphisms in the formation of OSAS in asthma patients. Overnight cardiorespiratory monitoring was performed to diagnose OSAS and spirometry was conducted to evaluate the airway reactivity to the bronchodilator fenoterol in 184 asthma patients. Polymorphisms of GAD1, GAD2, GABBR1 and GABBR2 genes (15 polymorphisms in total) were genotyped by LATE-PCR method. Significant results were obtained for rs3749034 polymorphism of GAD1 gene and rs35400353 of GABBR2 in association analysis with the presence of OSAS. rs3749034 significantly influenced the presence of OSAS in males, which was accompanied by the predominance of the CC genotype among patients with OSAS, while CT+TT genotypes were more common in patients without OSAS (OR 3.9 95%CI [1.36–11.67], p=0.01). In total sample GAD1 rs3749034 polymorphism was an independent factor increasing the likelihood of having OSAS after adjustment for significant confounders (OR 1.9 95%CI [1.23–3.15], p=0.005). rs35400353 polymorphism was also associated with OSAS after adjustment for confounders, although its relationship was less significant (OR 1.5 95%CI [1.1–2.3], p=0.04). There was a tendency for interrelation with airway hyperresponsiveness to bronchodilator for both polymorphisms: rs3749034 ‒ in case of CT+TT genotypes, rs35400353 ‒ in case of DD genotype. rs3749034 polymorphism also significantly influenced lung function parameters. After additional verification of the results, the identified genetic polymorphisms may be used to individually predict the risk of OSAS as well as for the development of personalized approaches in asthma treatment using GABA.

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Variation in PAH-related DNA adduct levels among non-smokers: The role of multiple genetic polymorphisms and nucleotide excision repair phenotype

International Journal of Cancer ◽

10.1002/ijc.27953 ◽

2012 ◽

Vol 132 (12) ◽

pp. 2738-2747 ◽

Cited By ~ 12

Author(s):

Arash Etemadi ◽

Farhad Islami ◽

David H. Phillips ◽

Roger Godschalk ◽

Asieh Golozar ◽

...

Keyword(s):

Genetic Polymorphisms ◽

Nucleotide Excision Repair ◽

Excision Repair ◽

Dna Adduct ◽

Nucleotide Excision

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“The Role of Epidemiology in the Investigation of Occupational Exposure as the Cause of Disease”

American Association of Industrial Nurses Journal ◽

10.1177/216507996601400105 ◽

1966 ◽

Vol 14 (1) ◽

pp. 19-21

Author(s):

Leonard M. Schuman

Keyword(s):

Occupational Exposure

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A18263 Role of obesity and genetic polymorphisms in the development of left ventricular hypertrophy among children with essential hypertension

Journal of Hypertension ◽

10.1097/01.hjh.0000549054.00325.37 ◽

2018 ◽

Vol 36 ◽

pp. e258

Author(s):

Olga Samarina ◽

Olga Kovtun ◽

Alexander Chuykov

Keyword(s):

Essential Hypertension ◽

Left Ventricular Hypertrophy ◽

Genetic Polymorphisms ◽

Ventricular Hypertrophy ◽

Left Ventricular

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Modification of the relationship between urinary 8-OHdG and hippuric acid concentration by GSTM1, GSTT1, and ALDH2 genotypes

Human & Experimental Toxicology ◽

10.1177/0960327110371813 ◽

2010 ◽

Vol 30 (4) ◽

pp. 338-342 ◽

Cited By ~ 3

Author(s):

Yong-Dae Kim ◽

Sang-Yong Eom ◽

Yan Wei Zhang ◽

Hyeongsu Kim ◽

Jung-Duk Park ◽

...

Keyword(s):

Dna Damage ◽

Occupational Exposure ◽

Genetic Polymorphisms ◽

Hippuric Acid ◽

Oxidative Dna Damage ◽

Statistical Significance ◽

Biological Marker ◽

Metabolizing Enzymes ◽

Toluene Exposure ◽

The Relationship

Urinary hippuric acid (HA) has been widely used as a biological marker of occupational exposure to toluene, although it is no longer valid for low levels of toluene exposure. Toluene exposure is known to induce oxidative DNA damage and the metabolism is affected by genetic polymorphisms of some metabolizing enzymes. Therefore, genetic polymorphisms of these metabolizing enzymes must be considered in the evaluation of oxidative stress caused by toluene exposure. We evaluated the relationship between urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and urinary HA in individuals without occupational exposure to toluene and characterized the possible roles of GSTM1, GSTT1, and aldehyde dehydrogenase 2 (ALDH2) genotypes in the relationships between these markers. In this study, we enrolled 92 healthy Koreans. Urinary HA and 8-OHdG levels were measured and the correlations between them were statistically tested according to the GSTM1, GSTT1, and ALDH2 genotypes. HA did not significantly correlate with urinary 8-OHdG in overall subjects. However, the correlation between them showed a statistical significance in individuals with GSTM1-null, GSTT1-null, and ALDH2 *2/*2 genotypes (r = 0.766, p < 0.01). This study shows that the relationship between urinary HA and 8-OHdG concentration is modified by genetic polymorphisms of some metabolizing enzymes such as GSTM1, GSTT1, and ALDH2.

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