Concentrations of Lead, Mercury, Arsenic, Cadmium, Manganese, and Aluminum in the Blood of Pakistani Children with and without Autism Spectrum Disorder and Their Associated Factors
Abstract
:1. Introduction
2. Materials and Methods
2.1. General Description
2.2. Study Design and Populations of ASD Cases and TD Controls
2.3. Sample Processing and Shipment
2.4. Assessment of Metal Exposures
2.5. Genetic Analysis
2.6. Data Management
2.7. Statistical Analysis
3. Results
4. Discussion
4.1. Association of Blood Metal Concentrations in Relation to ASD
4.2. Association of GST Genes in Relation to ASD
4.3. Interactive Association of GST Genes and Blood Concentrations of Heavy Metals in Relation to ASD
4.4. Blood Concentrations of Metals in Pakistani Children with and without ASD
5. Limitations
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | Categories | ASD Case N (%) | TD Control N (%) | Matched OR (95% CI) | p-Value | p-Value c |
---|---|---|---|---|---|---|
Child’s sex | Male | 24 (80.0) | 24 (80.0) | 1.00 (0.28, 3.54) | 1.00 | 1.00 |
Child’s age (months) | Age < 72 | 13 (43.3) | 13(43.3) | 1.00 (0.06, 15.99) | 1.00 | 1.00 |
Age ≥ 72 | 17 (56.7) | 17 (56.7) | ||||
Child’s ethnicity | Sindhi and Saraeki | 7 (23.3) | 6 (20.0) | 2.24 (0.32, 15.64) | 0.61 | 0.86 |
Punjabi | 5 (16.7) | 4 (13.3) | 2.37 (0.30, 18.60) | 0.58 | ||
Urdu speaking | 16 (53.3) | 16 (53.3) | 1.87 (0.33, 10.59) | 0.90 | ||
Other | 2 (6.67) | 4 (13.3) | ||||
Maternal age | <35 years | 23 (79.3) | 25 (89.3) | 2.00 (0.50, 8.00) | 0.33 | 0.33 |
(at child’s birth) | ≥35 years | 6 (20.7) | 3 (10.7) | |||
Paternal age | <35 years | 17 (58.6) | 20 (69.0) | 1.60 (0.52, 4.89) | 0.41 | 0.41 |
(at child’s birth) | ≥35 years | 12 (41.4) | 9 (31.0) | |||
Maternal ethnicity | Sindhi and Saraeki | 4 (13.3) | 5 (16.7) | 1.05 (0.16, 6.96) | 0.87 | 0.88 |
Punjabi | 4 (13.3) | 5 (16.7) | 1.01 (0.17, 6.11) | 0.80 | ||
Urdu speaking | 19 (63.3) | 16 (53.3) | 1.64 (0.33, 8.17) | 0.41 | ||
Other | 3 (10.0) | 4 (13.3) | ||||
Paternal ethnicity | Sindhi and Saraeki | 4 (13.3) | 7 (23.3) | 1.22 (0.16, 9.41) | 0.53 | 0.48 |
Punjabi | 5 (16.7) | 4 (13.3) | 2.48 (0.33, 18.89) | 0.51 | ||
Urdu speaking | 18 (60.0) | 13 (43.3) | 2.96 (0.54, 16.31) | 0.20 | ||
Other | 3 (10.0) | 6 (20.0) | ||||
Maternal education a | Up to high school | 1 (3.7) | 8 (28.6) | 10.4 (1.20, 90.09) | 0.02 | 0.02 |
(at child’s birth) | Beyond high school | 26 (96.3) | 20 (71.4) | |||
Paternal education a | Up to high school | 1 (3.6) | 6 (22.2) | 7.71 (0.86, 69.10) | 0.05 | 0.05 |
(at child’s birth) | Beyond high school | 27 (96.4) | 21 (77.8) | |||
Parental education | Both up to high school | 0 (0.0) | 5 (17.9) | NR b | 0.99 | 0.99 * |
(at child’s birth) | At least one beyond high school | 28 (100.0) | 23 (82.1) | |||
Socioeconomic status (SES) | Car ownership | 26 (86.7) | 28 (93.3) | 0.50 (0.09, 2.73) | 0.42 | 0.42 |
Home live in | Owned | 23 (76.7) | 21 (70) | 1.50 (0.42, 5.32) | 0.53 | 0.53 |
GSTT1de | I * | 24 (82.8) | 26 (86.7) | 0.80 (0.22,2.98) | 0.74 | 0.74 |
DD | 5 (17.2) | 4 (13.3) | ||||
GSTM1d | I * | 15 (50.0) | 18 (60.0) | 0.70 (0.27,1.84) | 0.47 | 0.47 |
DD | 15 (50.0) | 12 (40.0) | ||||
GSTP1 (codominant) | Ile/Ile | 14 (46.7) | 17 (56.7) | NR b | 1.00 | 0.87 * |
Ile/Val | 13 (43.3) | 13 (43.3) | 1.00 | |||
Val/Val | 3 (10.0) | 0 (0.0) | ||||
GSTP1 (dominant) | Ile/Ile | 14 (46.7) | 17 (56.7) | 0.67 (0.24, 1.87) | 0.44 | 0.44 |
Val/* | 16 (53.3) | 13 (43.3) |
Exposure Variables | Category | ASD Case N (%) | TD Control N (%) | MOR (95% CI) * | p-Value |
---|---|---|---|---|---|
Source of drinking water | Piped water | 4 (13.3) | 13 (43.4) | 0.18 (0.04, 0.82) | 0.03 |
Seafood | Lake/Pond fish (catfish, crappie) | 7 (23.3) | 12 (40.0) | 2.50 (0.69, 7.36) | 0.18 |
Bay fish (speckled trout, redfish, flounder) | 11 (36.7) | 8 (26.7) | 0.57 (0.17, 1.95) | 0.37 | |
River fish (bass, trout) | 7 (23.3) | 14 (46.7) | 2.75 (0.88, 8.64) | 0.08 | |
Offshore fish (tuna, snapper, whiting) | 5 (16.7)) | 5 (16.7) | 1.00 (0.25, 4.00) | 1.00 | |
Shellfish (lobster, crab, crawfish) | 3 (10.0) | 3 (10.0) | 1.00 (0.14, 7.10) | 1.00 | |
Meat/Organ | Beef as main dish | 18 (60.0) | 23 (76.7) | 2.25 (0.69, 7.31) | 0.18 |
Lamb as main dish | 2 (6.7) | 3 (10.0) | 1.50 (0.25, 8.98) | 0.66 | |
Goat as main dish | 24 (80.0) | 25 (83.3) | 1.25 (0.34, 4.66) | 0.74 | |
Chicken as main dish | 30 (100.0) | 28 (93.3) | NR ** | 1.00 | |
Liver, kidney | 4 (13.3) | 14 (46.7) | 4.33 (1.24, 15.21) | 0.02 | |
Dairy products/eggs | Milk | 25 (83.3) | 29 (96.7) | 5.80 (0.63, 53.01) * | 0.20 |
Yogurt | 11 (36.7) | 24 (80.0) | 5.33 (1.55, 18.30) | 0.01 | |
Eggs | 22 (73.3) | 29 (96.7) | 8.00 (1.00, 63.96) | 0.05 | |
Cheese | 8 (26.7) | 19 (63.3) | 6.50 (1.47, 28.80) | 0.01 | |
Root vegetables | Carrot, pumpkin | 12 (40.0) | 23 (76.7) | 4.67 (1.34, 16.24) | 0.02 |
Yam, sweet potato | 2 (6.7) | 11 (36.7) | 10.00 (1.28, 78.12) | 0.03 | |
Leafy vegetables | Lettuce | 10 (33.3) | 10 (33.3) | 1.00 (0.38, 2.66) | 1.00 |
Cauliflower, broccoli | 9 (30.0) | 17 (56.7) | 9.00 (1.14, 71.04) | 0.04 | |
Cabbage | 10 (33.3) | 15 (50.0) | 2.67 (0.71, 10.05) | 0.15 | |
Turnip | 4 (13.3) | 10 (33.3) | 3.00 (0.81, 11.08) | 0.10 | |
Spinach | 16 (53.3) | 15 (50.0) | 0.86 (0.29, 2.55) | 0.78 | |
Fruits | Oranges | 14 (46.7) | 26 (86.7) | 13.00 (1.70, 99.38) | 0.01 |
Tangerine | 7 (23.3) | 22 (73.3) | 8.50 (1.96, 36.79) | <0.01 | |
Grapes | 12 (40.0) | 26 (86.7) | 15.00 (1.98, 113.56) | <0.01 | |
Apples | 15 (50.0) | 27 (90.0) | 13.00 (1.70, 99.38) | 0.01 | |
Pineapples | 2 (6.7) | 9 (30.0) | 8.00 (1.00, 63.96) | 0.05 | |
Figs | 1 (3.3) | 7 (23.3) | 8.82 (1.01, 76.96) * | 0.05 | |
Peach | 6 (20.0) | 20 (66.7) | 5.67 (1.66, 19.34) | <0.01 | |
Plums | 3 (10.0) | 17 (56.7) | 15.00 (1.98, 113.56) | <0.01 | |
Strawberry | 6 (20.0) | 23 (76.7) | 9.50 (2.21, 40.79) | <0.01 | |
Blackberry | 1 (3.3) | 8 (26.7) | 8.00 (1.00, 63.96) | 0.05 | |
Banana | 22 (73.3) | 26 (86.7) | 5.00 (0.58, 42.80) | 0.14 | |
Watermelon | 10 (33.3) | 22 (73.3) | 7.00 (1.59, 30.80) | 0.01 | |
Other melon (cantaloupe, honeydew) | 10 (33.3) | 17 (56.7) | 2.40 (0.85, 6.81) | 0.10 | |
Other food related questions | Canned food | 6 (20.9) | 13 (43.3) | 4.50 (0.97, 20.83) | 0.05 |
Aluminum foil | 1 (3.3) | 1 (3.3) | 1.00 (0.06, 15.99) | 1.00 | |
Unpeeled fruits | 7 (23.3) | 19 (63.3) | 13.00 (1.70, 99.38) | 0.01 | |
Animal fat | 2 (6.7) | 0 (0.0) | NR ** | 1.00 |
Metal | Limits of Detection (LoD) | % Below LoD | Geometric Mean a (Based on Univariable GLMs) | Adjusted Geometric Mean a (Based on Multivariable Adjusted GLMs) * | ||||||
---|---|---|---|---|---|---|---|---|---|---|
ASD Cases | TD Controls | Mean Difference b | p Value c | ASD Cases | TD Controls | Mean Difference b | p Value c | |||
Al d | 5.0 μg/L | 83.3% | 4.05 | 3.92 | 0.13 | 0.68 | 4.49 | 3.69 | 0.80 | 0.06 |
As e | 1.3 μg/L | 66.7% | 1.15 | 1.12 | 0.03 | 0.74 | 1.47 | 1.29 | 0.18 | 0.30 |
Hg f | 0.25 μg/L | 51.7% | 0.29 | 0.29 | –0.00 | 0.96 | 0.24 | 0.20 | 0.05 | 0.40 |
Cd g | 0.13 μg/L | 43.3% | 0.14 | 0.15 | –0.00 | 0.84 | 0.16 | 0.16 | –0.00 | 0.88 |
Pb h | 0.25 μg/dL | 0.0% | 6.37 | 7.68 | –1.32 | 0.05 | 7.11 | 8.48 | –1.37 | 0.16 |
Mn i | 2.5 μg/L | 0.0% | 13.97 | 13.93 | 0.04 | 0.97 | 12.75 | 12.25 | 0.50 | 0.70 |
Metal | Binary | GSTT1 Genotype (s) a | Unadjusted b | Adjusted c | ||||
---|---|---|---|---|---|---|---|---|
Matched OR (95% CI) | p Value d | p-Value for GSTT1*Metal Interaction | Matched OR (95% CI) | p Value d | p-Value for GSTT1*Metal Interaction | |||
Pb | >50th vs. ≤50th | I * | 0.48 (0.15, 1.55) | 0.22 | 0.99 | 0.41 (0.12, 1.40) | 0.15 | 0.99 |
>50th vs. ≤50th | DD | NR | NR | NR | NR | |||
Mn | >50th vs. ≤50th | I * | 1.18 (0.30, 4.63) | 0.81 | 0.31 | 1.04 (0.26, 4.24) | 0.95 | 0.27 |
>50th vs. ≤50th | DD | 0.22 (0.01, 4.01) | 0.31 | 0.16 (0.01, 3.46) | 0.24 |
Metal | Binary | GSTP1 Genotype (s) a | Unadjusted b | Adjusted c | ||||
---|---|---|---|---|---|---|---|---|
Matched OR (95% CI) | p Value d | p Value for GSTP1*Metal Interaction | Matched OR (95% CI) | p Value d | p Value for GSTP1*Metal Interaction | |||
Pb | >50th vs. ≤50th | Val/* | 0.69 (0.16, 2.99) | 0.62 | 0.74 | 0.67 (0.15, 2.93) | 0.59 | 0.73 |
>50th vs. ≤50th | Ile/Ile | 0.48 (0.10, 2.41) | 0.38 | 0.46 (0.09, 2.35) | 0.35 | |||
Mn | >50th vs. ≤50th | Val/* | 0.57 (0.11, 3.06) | 0.51 | 0.40 | 0.56 (0.10, 3.06) | 0.50 | 0.53 |
>50th vs. ≤50th | Ile/Ile | 1.40 (0.29, 6.74) | 0.68 | 1.12 (0.22, 5.88) | 0.89 |
Metal | Binary | GSTM1 Genotype (s) a | Unadjusted a | Adjusted b | ||||
---|---|---|---|---|---|---|---|---|
Matched OR (95% CI) | p-Value c | p-Value for GSTM1*Metal Interaction | Matched OR (95% CI) | p-Value c | p-Value for GSTM1*Metal Interaction | |||
Pb | >50th vs. ≤50th | I * | 0.65 (0.16, 2.69) | 0.56 | 0.75 | 0.62 (0.15, 2.61) | 0.51 | 0.73 |
>50th vs. ≤50th | DD | 0.48 (0.10, 2.21) | 0.34 | 0.43 (0.09, 2.11) | 0.30 | |||
Mn | >50th vs. ≤50th | I * | 0.71 (0.15, 3.28) | 0.66 | 0.69 | 0.56 (0.11, 2.87) | 0.49 | 0.62 |
>50th vs. ≤50th | DD | 1.04 (0.23, 4.72) | 0.96 | 0.93 (0.20, 4.36) | 0.92 |
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Rahbar, M.H.; Ibrahim, S.H.; Azam, S.I.; Hessabi, M.; Karim, F.; Kim, S.; Zhang, J.; Gulzar Ali, N.; Loveland, K.A. Concentrations of Lead, Mercury, Arsenic, Cadmium, Manganese, and Aluminum in the Blood of Pakistani Children with and without Autism Spectrum Disorder and Their Associated Factors. Int. J. Environ. Res. Public Health 2021, 18, 8625. https://doi.org/10.3390/ijerph18168625
Rahbar MH, Ibrahim SH, Azam SI, Hessabi M, Karim F, Kim S, Zhang J, Gulzar Ali N, Loveland KA. Concentrations of Lead, Mercury, Arsenic, Cadmium, Manganese, and Aluminum in the Blood of Pakistani Children with and without Autism Spectrum Disorder and Their Associated Factors. International Journal of Environmental Research and Public Health. 2021; 18(16):8625. https://doi.org/10.3390/ijerph18168625
Chicago/Turabian StyleRahbar, Mohammad H., Shahnaz H. Ibrahim, Syed Iqbal Azam, Manouchehr Hessabi, Fatima Karim, Sori Kim, Jing Zhang, Nasreen Gulzar Ali, and Katherine A. Loveland. 2021. "Concentrations of Lead, Mercury, Arsenic, Cadmium, Manganese, and Aluminum in the Blood of Pakistani Children with and without Autism Spectrum Disorder and Their Associated Factors" International Journal of Environmental Research and Public Health 18, no. 16: 8625. https://doi.org/10.3390/ijerph18168625