Role of soluble alpha-klotho as a novel biomarker for characterizing children with autism spectrum disorder in Kurdistan, Iraq

doi:10.5409/wjcp.v15.i2.112164

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Jun 9, 2026 (publication date) through May 16, 2026

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World Journal of Clinical Pediatrics

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2219-2808

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Clin Pediatr. Jun 9, 2026; 15(2): 112164
Published online Jun 9, 2026. doi: 10.5409/wjcp.v15.i2.112164

Table 1 Demographic features for control and autism spectrum disorder groups

Demographic features	Control group		ASD group
Demographic features	Frequency	%	Frequency	%
Aged (year)
2-5	15	15	34	22
6-10	50	50	84	54
11-15	35	35	38	24
Sex
Boys	55	55	128	82
Girls	45	45	28	18
Family history
Yes	-	0	21	14
No	No	100	129	86
Experiencing complications at birth
Yes	31	31	83	53
No	69	96	73	47
Time of birth (weeks)
Early birth (< 37)	21	21	57	38
Normal birth (37-42)	67	67	42	28
Late birth (≥ 42)	12	12	51	34
Birth weight (kg)
Low (< 2.5)	8	8	49	33
Normal (2.5-4)	63	63	47	31
High (> 4)	19	19	54	36

ASD: Autism spectrum disorder.

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Table 2 Two-way analysis of variance

Source	Sum of squares	df	F-statistic	P value [PR (> F)]
C(Group)	31244.93	1.0	449.68	2.78e-46
C(Sex)	53603.79	1.0	771.46	6.36e-60
C(Group):C(Sex)	2500.74	1.0	35.99	1.51e-08
Residual	10075.08	145.0	NaN	NaN

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Table 3 Post-hoc testing (Tukey's honestly significant difference)

Post-hoc testing		Meandiff	P_adj value	Lower	Upper	Reject
Group
Group 1	Group 2
Control	Patient	-44.17	0.0	-51.482	-36.8579	True
Sex
Female	Male	-54.3757	0.0	-60.6834	-48.068	True
Group-sex interaction
Control_female	Control_male	-55.2969	0.0	-61.5194	-49.0744	True
Control_female	Patient_female	-45.1906	0.0	-52.0762	-38.305	True
Control_male	Patient_male	-25.8072	0.0	-30.6143	-21.0001	True
Patient_female	Patient_male	-35.9135	0.0	-41.5527	-30.2743	True

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Table 4 Sex bias adjustment and stratified analysis

	Source	Sum of squares	df	F-statistic	P value [PR (> F)]	Group 1	Group 2	Meandiff	P_adj value	Lower	Upper	Reject
ANOVA for males	C(Group)	13527.98	1.0	222.12	7.30e-28
ANOVA for males	Residual	6516.68	107.0	NaN	NaN
Post-hoc test (Tukey HSD) for males (group)						Control	Patient	-25.8072	0.0	-29.2399	-22.3745	True
ANOVA for females	C(Group)	20217.69	1.0	215.90	2.95e-17
ANOVA for females	Residual	3558.40	38.0	NaN	NaN
Post-hoc test (Tukey HSD) for females (group)						Control	Patient	-45.1906	0.0	-51.4167	-38.9645	True

HSD: Honestly significant difference.

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Table 5 Levels of soluble alpha-klotho by age in control and autism spectrum disorder patient groups, mean ± SD

Age (years)	Levels of S-KLα (pg/mL)
Age (years)	Control	Patients with ASD	P value
2-5	171.3 ± 23.5	129.3 ± 12.9	0.001
6-10	125.6 ± 18.1	89.4 ± 8.7	0.001
11-15	104.2 ± 16. 4	73.8 ± 8.4	0.001
Total	133.7 ± 32.4	97.5 ± 19.6	0.001
ANOVA, P value	0.001	0.001

ANOVA: Analysis of variance; ASD: Autism spectrum disorder; S-KLα: Soluble alpha-klotho.

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Table 6 Effect of some autism spectrum disorder patients’ characteristics on the concentration of (soluble alpha-klotho), mean ± SD

Characteristics	Levels of S-KLα (pg/mL)
Family history
Yes	94.8 ± 7.3
No	100.2 ± 8.2
Experiencing complications at birth
Yes	88.3 ± 7.1^a
No	106.7 ± 12.2
Time of birth (weeks)
Early birth (< 37)	95.7 ± 8.6^a
Normal birth (37-42)	106.3 ± 7.5^a
Late birth (≥ 42)	90.5 ± 9.1^a
Birth weight (kg)
Low (< 2.5)	98.2 ± 9.7
Normal (2.5-4)	100.7 ± 11.4
High (> 4)	93.6 ± 8.2

^aP < 0.001.

ASD: Autism spectrum disorder; S-KLα: Soluble alpha-klotho.

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Table 7 Clinical parameters for the control and autism spectrum disorder groups, mean ± SD

Parameters	ASD group	Controls group
Glucose, mg/dL	127.63 ± 17.47^a	98.13 ± 13.603
HGB, g/dL	10.45 ± 2.02^a	12.53 ± 2.81
Iron, μg/dL	63.33 ± 27.35^a	86.72 ± 20.697
Uric acid, mg/dL	3.24 ± 0.71^a	4.38 ± 0.82
Creatinine, mg/dL	0.45 ± 0.13	0.39 ± 0.09
Vit-D3, ng/mL	20.69 ± 13.87^a	32.93 ± 4.43

^aP ≤ 0.01.

ASD: Autism spectrum disorder; HGB: Hemoglobin; Vit-D3: Vitamin D3.

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Table 8 Receiver operating characteristic analysis results of soluble alpha-klotho for autism spectrum disorder prediction

Parameters	Area under the curve	SE¹	Asymptotic sig²	Asymptotic 95%CI		Cut off value	Sensitivity	Specificity	Youden index
Parameters	Area under the curve	SE¹	Asymptotic sig²	Lower bound	Upper bound	Cut off value	Sensitivity	Specificity	Youden index
S-KLα	0.91	0.0225	0.001	0.866	0.954	120 pg/mL	0.822	0.94	0.76
Vit-D3	0.9	0.0224	0.000	0.85	0.94	37.3 ng/mL	0.8	0.76	0.8
Creatinine	0.66	0.0381	0.000	0.58	0.74	0.48 mg/dL	0.93	0.81	0.35
Glucose	0.97	0.0118	0.000	0.94	0.99	99 mg/dL	0.98	0.75	0.86
Uric acid	0.92	0.0198	0.000	0.88	0.96	5.1 mg/dL	0.93	0.72	0.65
Iron	0.87	0.0256	0.000	0.87	0.92	86 μg/dL	0.8	0.81	0.61
HGB	0.79	0.0316	0.000	0.73	0.85	12.3 g/dL	0.56	0.48	0.48
Age	0.58	0.0400	0.037	0.51	0.67	10 years	0.62	0.53	0.15

¹Under the nonparametric assumption.

²Null hypothesis: True area = 0.5.

CI: Confidence interval; HGB: Hemoglobin; SE: Standard error; S-KLα: Soluble alpha-klotho; Vit-D3: Vitamin D3.

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Table 9 Multiple logistic regression for soluble alpha-klotho with clinical and demographic variables about autism spectrum disorder

Variable	Coefficient	SE	Z value	P value	Odds ratio	CI lower	CI upper	Model
S-KLα	-2.582525408	0.070534562	-36.61361679	< 0.001	0.075582885	0.065823843	0.086788803	Crude S-KLα
S-KLα	-1.106053775	0.070534562	-15.68101864	< 0.001	0.330862044	0.288142101	0.379915646	Adjusted
Glucose	2.146374519	0.070534562	30.43011073	< 0.001	8.553790512	7.449349988	9.821975371	Adjusted
HGB	-0.843398629	0.070534562	-11.95723926	< 0.001	0.43024579	0.374693706	0.494034025	Adjusted
Iron	-0.956778886	0.070534562	-13.56468183	< 0.001	0.384128216	0.334530699	0.44107906	Adjusted
Uric acid	-1.331937581	0.070534562	-18.8834743	< 0.001	0.263965311	0.229882879	0.303100805	Adjusted
Creatinine	0.338779702	0.070534562	4.803031227	< 0.001	1.403234181	1.22205267	1.611277661	Adjusted
Vit-D3	-1.120827901	0.070534562	-15.89047802	< 0.001	0.326009779	0.283916346	0.374343984	Adjusted
Age	-0.107553476	0.070534562	-1.524833696	0.127	0.898028498	0.782077673	1.03117019	Adjusted
Time birth	-0.177124829	0.070534562	-2.511177856	0.012	0.837675212	0.729517028	0.961868927	Adjusted
Weight birth	-0.00716277	0.070534562	-0.101549787	0.919	0.992862822	0.864667265	1.14006465	Adjusted

CI: Confidence interval; HGB: Hemoglobin; SE: Standard error; S-KLα: Soluble alpha-klotho; Vit-D3: Vitamin D3.

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Table 10 Correlation between soluble alpha-klotho and parameters in autism spectrum disorder groups by using Pearson’s coefficient

		S-KLα, pg/mL	Glucose, mg/dL	HGB, g/dL	Iron, ug/dL	Uric acid, mg/dL	Creatinine, mg/dL	Vit-D3, ng/mL	Age, year	Time of birth, weeks	Birth weight, kg
S-KLα, pg/mL	R	1	-0.491¹	0.551¹	0.578¹	0.310	0.220	0.701¹	0.071	0.173	0.037
S-KLα, pg/mL	Sig (2-tailed)		0.001	0.001	0.001	0.032	0.021	0.001	0.484	0.086	0.718

¹Correlation is significant at the 0.01 level (two-tailed).

HGB: Hemoglobin; R: Pearson correlation; S-KLα: Soluble alpha-klotho; Vit-D3: Vitamin D3.

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Citation: Allwsh TA, Kucher DS. Role of soluble alpha-klotho as a novel biomarker for characterizing children with autism spectrum disorder in Kurdistan, Iraq. World J Clin Pediatr 2026; 15(2): 112164
URL: https://www.wjgnet.com/2219-2808/full/v15/i2/112164.htm
DOI: https://dx.doi.org/10.5409/wjcp.v15.i2.112164

Allwsh TA, Kucher DS. Role of soluble alpha-klotho as a novel biomarker for characterizing children with autism spectrum disorder in Kurdistan, Iraq. World J Clin Pediatr 2026; 15(2): 112164 [DOI: 10.5409/wjcp.v15.i2.112164]

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