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The basic clinical and exposure data of the study participants (all male) are shown in Table 1. The statistical findings showed that there is no significant difference in age, BMI, daily exposure time, job history, and smoking history between the case and control groups. Regarding the case group, they had a mean age of 34.26 years (with a range of 21–58 years) and a mean exposure period of 11.8 hours (range of 8–16 h) over a job span of 7.38 years (range of 2–20 years). Moreover, their average BMI was 25.85 kg/m2 (range of 16.48–35.83 kg/m2) and 5.3 % of them had a history of smoking. The above information for the control group was as follows; a mean age of 34.47 years (with a range of 24–51 years), a mean exposure period of 11.66 hours (range of 4–15 h) over a job span of 7.84 years (range of 2–24), a mean BMI of 25.85 kg/m2 (range of 18.6–33.9 kg/m2), and 5.8% of them were smokers.
Variables Case (n=138) Control (n=145) P-values Age (years), mean ± SD 34.26 ± 6.50 34.47 ± 5.36 0.67 BMI (kg/m2), mean ± SD 25.85 ± 3.38 25.40 ± 4.78 0.84 Length of exposure in a day (hours), mean ± SD 11.80 ± 1.44 11.66 ± 1.45 0.45 Job history (year), mean ± SD 7.38 ± 3.75 7.84 ± 4.16 0.47 Smoking, n (%) 0.87 Yes 7 (5.3) 8 (5.8) NO 125 (94.7) 131 (94.2) BTEX-exposure measurements (ppm), mean ± SD Benzene 0.57 ± 1.51 0.71 ± 1.59 0.99 Toluene 1.02 ± 2.03 1.11 ± 2.17 0.88 Ethylbenzene 1.44 ± 2.52 1.24 ± 2.70 0.27 O-xylene 0.437 ± 1.33 0.414 ± 1.64 0.27 P-xylene 2.47 ± 3.06 2.28 ± 3.04 0.49 M xylene 1.70 ± 2.46 1.79 ± 2.64 0.89 Note. Student’s t-test was used to determine the statistical significance of the differences in age, BMI, daily exposure time, and job history, and the chi-square test was used for smoking history; P-value < 0.05 was considered statistically significant (in bold). BMI, body mass index; BTEX, benzene toluene ethylbenzene xylene. *Some data were missing due to lack of information. Table 1. Characteristics of the BTEX and other variables in two groups of the study participants.
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As mentioned in the previously, in this study we measured the concentration of each of the BTEX components in the breathing air environment of the study participants to evaluate the exposure. The results of this assessment showed that the mean of arithmetic concentrations of benzene, toluene, and ethylbenzene in the air environment of the population was 0.70 (standard deviation = 1.67 ppm), 1.10 (standard deviation = 2.14 ppm), and 1.34 (standard deviation = 2.6 ppm), respectively. Moreover, the composition of xylene is considered as a set mixture of ortho, para, and meta isomers whose average concentrations were 0.44 (standard deviation = 1.48 ppm), 2.36 (standard deviation = 3.04), and 1.75 (standard deviation = 2.54 ppm), respectively. The findings also showed that there was no significant difference in the concentrations of various BTEX compounds in the breathing environments of both patients and healthy individuals (Table 1).
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As shown in Table 2, a significant difference was observed in the levels of some blood indices between the two study groups. The mean RDW and lymphocyte count were significantly higher in patients than in healthy controls (P = 0.018 and P = 0.001, respectively). The mean HB, MCV, MCH, MCHC, and granulocyte counts revealed a significant decrease in the case group compared to the control group (P = 0.001, P = 0.004, P = 0.001, P = 0.002, and P = 0.001, respectively). Other blood indices, including HCT, WBC, RBC, PLT count, and monocyte count, were not significantly different between the two groups. Additionally, regarding the RBC-related indices, including RBC count, HB, MCV, HCT, MCH, mean MCHC, and red RDW, it was found that their abnormalities in patients was 15.21%, 22.46%, 13.76%, 21.01%, 25.36%, 23.18%, and 9.42%, respectively. Moreover, 7.20% of the case group showed abnormal WBC index. The abnormality rates for lymphocytes, monocytes, and granulocytes was 62.31%, 10.86%, and 8.69%, respectively. For the platelet index, we observed a 10.14% aberration (Supplementary Tables, available in www.besjournal.com).
Hematological indices Case (n = 138) Control (n=145) P-values WBC (×109/L) 6.97 ± 1.86 7.03 ± 1.51 0.80 RBC (×109/L) 5.04 ± 0.559 5. 0 ± 0.360 0.47 HB (g/dL) 14.77 ± 1.50 15.32 ± 0.840 0.001 HCT (%) 43.52 ± 3.65 44.22 ± 2.24 0.051 MCV (fL) 86.20 ± 9.30 88.67 ± 3.82 0.004 MCH (Pg) 29.64 ± 3.67 30.75 ± 1.71 0.001 MCHC (g/dL) 34.10 ± 1.89 34.66 ± 0.911 0.002 RDW (%) 12.41 ± 0.968 12.13 ± 0.562 0.018 Platelets (×109/L) 212 ± 46.64 210.8 ± 38.52 0.908 Lymphocytes (%) 44.72 ± 10.87 37.96 ± 5.72 0.001 Monocytes (%) 2.92 ± 1.59 3.08 ± 1.79 0.936 Granulocytes (%) 51.07 ± 10.68 57.97 ± 6.38 0.001 Note. Values are given as the mean ± standard deviation; Student t-test for comparing the difference of hematological indices in the case and control groups was used; P-value <0.05 was considered statistically significant (in bold). WBC, white blood cell count; RBC, red blood cell count; HB, hemoglobin; HCT, hematocrit; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; RDW, red cell distribution width. Table 2. Data on hematological indices in case and control subjects
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As described in Table 3, in the current population, the genotype frequencies of miR-100-rs543412 C>T in the cases and controls were consistent with HWE (P > 0.05), whereas the genotypes of miR-506-rs5905008 A>G were not in equilibrium (P > 0.05). Regarding the comparison of allelic and genotype frequencies of miR-100-rs543412 C>T polymorphism between the two groups, we observed that patients differ from healthy individuals in both allelic (P = 0.005) and genotype (P = 0.013) frequencies, in which the patient group carried significantly fewer T minor allele (39.5% vs. 51.4 %, P = 0.005) and TT minor genotype (13.8% vs. 24.1%, P = 0.013) compared with the healthy group.
SNPs Cases (n=138),
N (%)Controls (n=145)
N (%)P-Value P-HWE miR-100-rs543412c>T Genotypes
CC
CT
TT
48(34.8)
71(51.4)
19(13.8)
31(21.4)
79(54.5)
35(24.1)
0.013
0.24Alleles
C
T
167(60.5)
109(39.5)
141(48.6)
149(51.4)0.005 miR-506-rs5905008a>G
Genotypes
AA
AG
GG
21(15.2)
17(12.3)
100(72.5)
23(15.9)
23(15.9)
99(68.3)
0.66
0.001Alleles
A
G
217(78.6)
59(21.4)
221(76.2)
69(23.8)
0.49Note. Person χ2 test used for difference in distributions between the case and control groups. A goodness-of-fit chi-squared test was used to evaluate the Hardy-Weinberg equilibrium in the study. population; P-value < 0.05 was considered statistically significant (in bold). SNPs, single nucleotide polymorphisms; P-HWE, P value for Hardy-Weinberg equilibrium. Table 3. Genotype and allele distribution of the selected polymorphisms in study population groups.
We also used multiple genetic models of inheritance by regression analysis to determine the risk or protective relationship of each allele and genotype of this SNP with abnormalities in blood indices in the exposed subjects (Table 4). It was observed that TT and CT genotypes of the rs543412 C > T was significantly associated with the decreased risk of abnormal blood indices under genetic models of codominant (CT vs. CC, OR: 0.546, 95% CI: 0.312–0.957, P = 0.034 & TT vs. CC, OR: 0.335, 95% CI: 0.158–0.711, P = 0.004), dominant (CT+TT vs. CC, OR: 0.486, 95% CI: 0.285–0.830, P = 0.008), and recessive (TT vs. CC+CT, OR: 0.507, 95% CI: 0.267–0.962, P = 0.038). It should be noted that this finding was maintained in both the adjusted (for variables of age, BMI, smoking, and length of exposure to BTEXs) and unadjusted states, except for the CT heterozygous genotype in the codominant model, which was not significant, with a borderline value (P = 0.054). Finally, we conducted further stratification analyses to evaluate the independent effect of each genotype on each hematological parameter in BTEX-exposed workers, and the findings were not significant for any subgroup (Supplementary Tables).
SNPs Genotype models Genotypes Population groups Unadjusted OR (95%CI) P Adjusted OR (95%CI) P Case (n = 138) Control (n = 145) miR-100-RS543412C>T Codominant C/CC/TT/T 48 (34.8%) 31 (21.4%) 1 1 71 (51.4%) 79 (54.5%) 0.580 (0.334-1.010) 0.054 0.546 (0.312-0.957) 0.034 19 (13.8%) 35 (24.1%) 0.351 (0.171-0.719) 0.004 0.335 (0.158-0.711) 0.004 Dominant C/CC/T+T/T 48 (34.8%) 31 (21.4%) 1 1 90 (65.2%) 114 (78.6%) 0.510 (0.300-0.866) 0.013 0.486 (0.285-0.830) 0.008 Recessive C/C+C/TT/T 119 (86.2%) 110 (75. 9%) 1 1 19 (13.8%) 35 (24.1%) 0.502 (0.271-0.929) 0.028 0.507 (0.267-0.962) 0.038 Overdominant C/C+T/TC/T 67 (48.6%) 66 (45.5%) 1 1 71 (51.4%) 79 (54.4%) 0.885 (0.555-1.413) 0.609 0.822 (0.510 -1.325) 0.421 miR-506-RS5905008A>G Codominant A/AA/GG/G 21 (15.2%) 23 (15.9%) 1 1 17 (12.3%) 23 (15.9%) 0.732 (0.369 -1.453) 0.37 0.684 (0.339 -1.379) 0.28 100 (72.5%) 99 (68.3%) 0.904 (0.470 -1.738) 0.76 0.893 (0.457 -1.745) 0.74 Dominant A/AA/G+G/G 21 (15.2%) 23 (15.9%) 1 1 117 (84.8%) 122 (84.1%) 0.952 (0.500 -1.812) 0.88 0.933 (0.482 -1.804) 0. 83 Recessive A/A+A/GG/G 38 (27.5%) 46 (31.7%) 1 100 (72.5%) 99 (68.3%) 0.818 (0.490 -1.364) 0.44 0.780 (0.463 -1.315) 0. 35 Overdominant A/A+G/GA/G 121 (87.7%) 122 (84.1%) 1 1 17 (12.3%) 23 (15.9%) 0.745 (0.379 -1.464) 0.39 0.702 (0.352 -1.399) 0.31 Note. OR, Odds ratio; 95% CI, 95% confidence interval; P < 0.05, considered statistically significant; logistic regression model, OR adjusted for age, BMI, smoking and length of exposure to benzene. Table 4. Association results between miR-SNP genotypes and patterns of hematological parameters in multiple inheritance models.
No significant differences were observed in the genotype and allele frequencies of the miR-506-rs5905008 A>G SNP between subjects with abnormal hematological indices and healthy controls. In addition, we did not find significant statistical values for the regression analysis data under different genetic models or for the results of its relationship with each subgroup of blood parameters. Nevertheless, when the combined genotypes of the miR-100-rs543412 C>T and miR-506-rs5905008 A>G polymorphisms were compared between the two groups using combined genotype analysis, it was revealed that the combined heterozygote genotype of the two SNPs was significantly different (P = 0.028) between the two groups and was associated with a reduced risk of blood index abnormalities (OR: 0.089, 95% CI: 0.009–0.857, P = 0.03) (Table 5).
Combined genotypes N (%) Cases Controls P-value OR (95%CI) P-value CCAA 17 (6.0) 9 (6.5) 8 (5.5)
0/028ref − CCAG 10 (3.5) 6 (4.3) 4 (2.8) 1.33 (0.274-6.49) 0.99 CCGG 52 (18.4) 33 (23.9) 19 (13.1) 1.544 (0.510- 4.670) 0.44 CTAA 16 (5.7) 11 (8.0) 5 (3.4) 1.956 (0.471- 8.11) 0.35 CTAG 25 (8.8) 9 (6.5) 16 (11.0) 0.089 (0.009- 0.857) 0.03 CTGG 109 (38.5) 51 (37.0) 58 (40.0) 0.500 (0.143- 1.753) 0.27 TTAA 11 (3.9) 1 (0.7) 10 (6.9) 0.782 (0.281- 2.176) 0.63 TTAG 5 (1.8) 2 (1.4) 3 (2.1) 0.593 (0.078- 4.498) 0.61 TTGG 38 (13.4) 16 (11.6) 22 (15.2) 0.646 (0.205- 2.041) 0.45 Note. Logistic regression model, OR, odds ratio, 95% CI 95% confidence interval P < 0.05 considered statistically significant. Table 5. The results of the combined genotype analysis of the two polymorphisms under study.
A miR-100 Polymorphism Signature is Protectively Associated with Hematological Abnormalities in Individuals Exposed to Benzene, Toluene, Ethylbenzene, and Xylene
doi: 10.3967/bes2024.110
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Key words:
- BTEX compounds /
- Genetic susceptibility /
- miR-100 SNP /
- rs543412C>T /
- Hematological abnormalities
Abstract:
&These authors contributed equally to this work.
Citation: | Farnaz Nourmohammadian Dehkordi, Samaneh Jafari Roshan, Amin Yousefvand, Behnam Mansoori, Yaser Mansoori, Abdolreza Daraei. A miR-100 Polymorphism Signature is Protectively Associated with Hematological Abnormalities in Individuals Exposed to Benzene, Toluene, Ethylbenzene, and Xylene[J]. Biomedical and Environmental Sciences. doi: 10.3967/bes2024.110 |