Killer-cell immunoglobulin-like receptors associated with polycystic ovary syndrome

Laise Nayana Sala Elpidio; Josiane Bazzo de Alencar; Patrícia Yumeko Tsuneto; Hugo Vicentin Alves; Mariana Trento Toretta; Sérgio Ken It Taura; Jeane Eliete Laguila Visentainer; Ana Maria Sell

doi:10.1016/j.jri.2018.08.003

Killer-cell immunoglobulin-like receptors associated with polycystic ovary syndrome

J Reprod Immunol. 2018 Nov:130:1-6. doi: 10.1016/j.jri.2018.08.003. Epub 2018 Aug 4.

Authors

Laise Nayana Sala Elpidio¹, Josiane Bazzo de Alencar¹, Patrícia Yumeko Tsuneto¹, Hugo Vicentin Alves¹, Mariana Trento Toretta², Sérgio Ken It Taura³, Jeane Eliete Laguila Visentainer⁴, Ana Maria Sell⁵

Affiliations

¹ Postgraduate Program in Biosciences and Physiopathology at the State University of Maringá, Paraná, Brazil.
² Biologic Science Department, State University of Maringá, Paraná, Brazil.
³ Health Department of Maringá, Paraná, Brazil; The State University of Maringá, Brazil.
⁴ Postgraduate Program in Biosciences and Physiopathology at the State University of Maringá, Paraná, Brazil; Laboratory of Immunogenetics, State University of Maringá, Paraná, Brazil.
⁵ Postgraduate Program in Biosciences and Physiopathology at the State University of Maringá, Paraná, Brazil; Laboratory of Immunogenetics, State University of Maringá, Paraná, Brazil. Electronic address: anamsell@gmail.com.

PMID: 30099219
DOI: 10.1016/j.jri.2018.08.003

Abstract

Polycystic ovary syndrome (PCOS) affects the endocrine system and is associated with low-grade inflammation. Natural killer (NK) cells are involved in the defense of the female reproductive tract, folliculogenesis, ovulation and the menstrual cycle. The killer-cell immunoglobulin-like receptors (KIR) on the surface of NK cells modulate the activation and function of these cells after interacting with human leukocyte antigen (HLA) class I ligands. The objective of this study was to evaluate the possible association of the KIR and their HLA ligands with polycystic ovary syndrome.

Methods: Ninety-three patients with PCOS according to the Rotterdam criteria and 104 healthy controls were included in this study. The HLA class I and KIR genotypes were determined using a PCR-SSO technique, rSSO Luminex®. In order to assess whether the distribution of the HLA and KIR genotypes was in Hardy-Weinberg equilibrium, Arlequin 3.1 software was used. The frequency distributions in the two study groups were compared using the chi-squared statistic with Yates´s correction using Open Epi software.

Results: The higher frequencies of KIR3DS1-Bw4 (41% vs. 19%, Pc = 0.002; OR = 2.90) and homozygotic KIR2DS4-del (54% vs. 26%, Pc = 0.0002; OR = 3.316) in patients compared with controls suggest they confer susceptibility to PCOS. A lower frequency of KIR2DS4-full was observed in patients (43% vs. 70%, Pc = 0.0004, OR = 0.320).

Conclusion: KIR and its HLA ligands were associated with the development of PCOS in the studied population.

Keywords: Genetic association studies; HLA antigens; KIR receptor; Natural killer cells; Polycystic ovary syndrome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Case-Control Studies
Epitopes / genetics
Epitopes / immunology
Female
Gene Frequency
Genetic Predisposition to Disease*
Genotyping Techniques
Histocompatibility Antigens Class I / immunology
Histocompatibility Antigens Class I / metabolism
Homozygote
Humans
Killer Cells, Natural / immunology*
Killer Cells, Natural / metabolism
Polycystic Ovary Syndrome / genetics*
Polycystic Ovary Syndrome / immunology
Receptors, KIR / genetics*
Receptors, KIR / immunology
Receptors, KIR3DS1 / genetics*
Receptors, KIR3DS1 / immunology
Young Adult

Substances

Epitopes
Histocompatibility Antigens Class I
KIR2DS4 protein, human
KIR3DS1 protein, human
Receptors, KIR
Receptors, KIR3DS1