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Original Research: SLEEP MEDICINE |

Leptin and Leptin Receptor Gene Polymorphisms in Obstructive Sleep Apnea Syndrome*

Masayuki Hanaoka, MD, PhD; Xiujun Yu, MD, PhD; Kazuhisa Urushihata, MD; Masao Ota, PhD; Keisaku Fujimoto, MD, PhD; Keishi Kubo, MD, PhD, FCCP
Author and Funding Information

*From the First Department of Medicine (Drs. Hanaoka, Yu, Urushihata, Fujimoto, and Kubo) and Department of Legal Medicine (Dr. Ota), Shinshu University School of Medicine, Matsumoto, Japan.

Correspondence to: Masayuki Hanaoka, MD, PhD, First Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan; e-mail: masayuki@hsp.md.shinshu-u.ac.jp



Chest. 2008;133(1):79-85. doi:10.1378/chest.07-1633
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Background: Obstructive sleep apnea is common in obese people. Leptin is an adipocyte-derived signaling factor that has an important role in metabolic control. There is growing evidence that leptin regulation is altered in obstructive sleep apnea syndrome (OSAS). The aim of this study was to investigate the relation between polymorphisms of the leptin and leptin receptor (LEPR) genes and OSAS.

Methods: The study population consisted of 130 patients with OSAS and 50 healthy control subjects. All the subjects were Japanese. Diagnostic polysomnography was performed in all patients and control subjects. A highly polymorphic tetranucleotide repeat polymorphism in the 3′-flanking region of the leptin gene and three single nucleotide polymorphisms (SNPs) [Lys109Arg (A/G) in exon 4, Gln223Arg (A/G) in exon 6, and Lys656Asn (G/C) in exon 14] in the LEPR gene were examined.

Results: There were no significant differences in allelic frequencies and genotype distributions of the examined polymorphisms of the leptin and LEPR genes between OSAS patients and control subjects. For the LEPR gene, the wild-type alleles of the Gln223Arg and Lys656Asn SNPs had a marginally significant effect on mild OSAS, which was defined as an apnea-hypopnea index from 10 and 20 events/h in the dominant model.

Conclusions: The tetranucleotide repeat polymorphism of the leptin gene and the Lys109Arg, Gln223Arg, and Lys656Asn SNPs in the LEPR gene were not associated with OSAS in the Japanese population. Further studies are required to confirm the association of the wild types of Gln223Arg and Lys656Asn SNPs with the severity of OSAS.

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