Malectin gene polymorphisms promote cerebral palsy via
M2-like macrophage polarization
| Y. Zhu
| M. Zhou
| Y. Ruan
| X. Chen
| X. Chen
Central Laboratory, Taizhou Hospital of
Zhejiang Province, Taizhou, China
Prenatal Diagnosis Center, Taizhou Hospital
of Zhejiang Province, Taizhou, China
Weiwu Shi, MD, PhD, Central Laboratory,
Taizhou Hospital of Zhejiang Province,
371000, Zhejiang, China.
The relationship between gene polymorphisms and the pathogenesis of cerebral palsy (CP) is
uncovering recently. Here, we suggested that single nucleotide polymorphisms (SNPs) of MLEC
gene might take part in the pathogenesis of CP. We genotyped and analyzed 6 SNP positions
of MLEC gene in 916 CP patients and 957 healthy people, which are from the Chinese Han
population. The results indicated significant associations between the risk of CP and
rs10431386 [allele: P-value = .006, odds ratio (OR) = 1.587, 95% confidence interval
(CI) = 1.198-1.967] and rs7964786 [allele: P-value = .005, OR = 1.956, 95% CI = 1.238-2.519]
SNP positions of MLEC gene. Further investigations revealed that C alleles of rs10431386 and
rs7964786 inhibit the expression of MLEC in blood of CP patients and macrophage cell line.
in vitro experiments revealed that MLEC promotes M1 to M2 macrophage polarization. The
results of in vitro studies suggest that C alleles of rs10431386 and rs7964786 on MLEC pro-
motes CP by inhibiting M1 to M2 macrophage polarization. Generally, this work suggested the
contribution of MLEC gene polymorphisms to the pathogenesis of CP.
cerebral palsy, MLEC, SNP
1 | INTRODUCTION
Cerebral palsy (CP) is a neurological disorder that is attributed to
non-progressive injury or malformation that occurred in the develop-
ing fetal or infant brain.
It’s a group of permanent disorders of the
development of movement and posture that appear in early child-
The approximate prevalence of CP −2 to 2.5 cases per 1000
births—has been stable for more than 4 past decades.
CP is the
leading cause of children physical disability and is the costliest clini-
cally birth defects worldwide.
Perinatal, postnatal, and most important prenatally risk factors,
which are the majority of about 70% to 80%, are categorized for CP.
Prenatal inflammations are important causal factors for adverse neuro-
The M1/M2 macrophage polarization plays impor-
tant roles in regulating inflammatory responses of the immune system.
M1 macrophages are neurotoxic and maintained for weeks post-injury
after occurrence of hypoxic-ischemic encephalopathy (HIE), a type of
brain damage in CP. On the other side, M2 macrophages are not
neurotoxic and promote neuron repair by stimulating long-distance
which will relieve multiple CP symptoms.
Malectin (MLEC) is a carbohydrate-binding protein malectin,
which is a Type I membrane-anchored endoplasmic reticulum
and interacts directly with embryonic lethal abnormal
vision (ELAV) like RNA binding protein 1 (ELAVL1),
a regulator of
If 2 proteins interact with each other,
they may have shared functions.
It implied that MLEC may also
play roles in CP via macrophage polarization. In this study, we geno-
typed and analyzed single nucleotide polymorphisms (SNPs) positions
in the MLEC gene in 916 CP patients and 957 healthy people, which
are from the Chinese Han population, to investigate the potential
relationship between MLEC and CP. The results suggested interactive
effects of rs10431386 and rs7964786 on the risk of CP. Further
investigations revealed that C alleles of rs10431386 and rs7964786
inhibit the expression of MLEC to inhibit M1 to M2 macrophage
polarization. This work is the first one to discover the potential con-
tribution of MLEC gene polymorphisms to the pathogenesis of CP.
Received: 11 September 2017 Revised: 22 September 2017 Accepted: 26 September 2017
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
794 wileyonlinelibrary.com/journal/cge Clinical Genetics. 2018;93:794–799.