Cyclooxygenase-2 (COX-2) polymorphism rs689466 may contribute to the increased susceptibility to post-traumatic osteomyelitis in Chinese population

Abstract

Background: Cyclooxygenase-2 (COX-2) enzyme is one of the major mediators during inflammation reactions, and COX-2 gene polymorphisms of rs20417 and rs689466 have been reported to be associated with several inflammatory diseases. However, potential links between the two polymorphisms and risk of developing post-traumatic osteomyelitis remain unclear. The present study aimed to investigate associations between the rs20417 and rs689466 polymorphisms and susceptibility to post-traumatic osteomyelitis in Chinese population.
Methods: A total of 189 patients with definite diagnosis of post-traumatic osteomyelitis and 220 healthy controls were genotyped for rs20417 and rs689466 using the SNaPshot genotyping method. Chi-square test was used to compare differences of genotype distributions as well as outcomes of five different genetic models between the two groups.
Results: Significant association was found between rs689466 and post-traumatic osteomyelitis by recessive model (GG vs AA + AG) (OR = 1.74, 95% CI 1.098 – 2.755, P = 0.018). Although no statistical differences were identified of rs689466 between the two groups by allele model (P = 0.098) or homozygous model (P = 0.084), outcomes revealed a tendency that allele G may be a risk factor and people of GG genotype may be in a higher risk to develop post-traumatic osteomyelitis in Chinese population. However, no significant link was found between rs20417 and susceptibility to post-traumatic osteomyelitis in this Chinese cohort.
Conclusions: To our knowledge, we reported for the first time that COX-2 gene polymorphism rs689466 may contribute to the increased susceptibility to post-traumatic osteomyelitis in Chinese population.

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Infectious Diseases
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Cyclooxygenase-2 (COX-2) polymorphism rs689466
may contribute to the increased susceptibility
to post-traumatic osteomyelitis in Chinese
population
Lei Wang, Nan Jiang, Qing-rong Lin, Cheng-he Qin, Yan-jun Hu & Bin Yu
To cite this article: Lei Wang, Nan Jiang, Qing-rong Lin, Cheng-he Qin, Yan-jun Hu & Bin Yu
(2017) Cyclooxygenase-2 (COX-2) polymorphism rs689466 may contribute to the increased
susceptibility to post-traumatic osteomyelitis in Chinese population, Infectious Diseases, 49:11-12,
817-823, DOI: 10.1080/23744235.2017.1347816
To link to this article: http://dx.doi.org/10.1080/23744235.2017.1347816
Published online: 06 Jul 2017.
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INFECTIOUS DISEASES,
2017; VOL. 49,
NO. 11-12, 817–823
https://doi.org/10.1080/23744235.2017.1347816
ORIGINAL ARTICLE
Cyclooxygenase-2 (COX-2) polymorphism rs689466
may contribute to the increased susceptibility to
post-traumatic osteomyelitis in Chinese population
Lei Wang
a
, Nan Jiang
a,b
, Qing-rong Lin
a
, Cheng-he Qin
a
, Yan-jun Hu
a
and Bin Yu
a,b
a
Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China;
b
Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical
University, Guangzhou, PR China
ABSTRACT
Background: Cyclooxygenase-2 (COX-2) enzyme is one of the major mediators during inflammation reactions, and COX-2
gene polymorphisms of rs20417 and rs689466 have been reported to be associated with several inflammatory diseases.
However, potential links between the two polymorphisms and risk of developing post-traumatic osteomyelitis remain
unclear. The present study aimed to investigate associations between the rs20417 and rs689466 polymorphisms and sus-
ceptibility to post-traumatic osteomyelitis in Chinese population.
Methods: A total of 189 patients with definite diagnosis of post-traumatic osteomyelitis and 220 healthy controls were gen-
otyped for rs20417 and rs689466 using the SNaPshot genotyping method. Chi-square test was used to compare differences
of genotype distributions as well as outcomes of five different genetic models between the two groups.
Results: Significant association was found between rs689466 and post-traumatic osteomyelitis by recessive model (GG vs.
AA þAG) (OR ¼1.74, 95% CI: 1.098–2.755, p¼.018). Although no statistical differences were identified of rs689466 between
the two groups by allele model (p¼.098) or homozygous model (p¼.084), outcomes revealed a tendency that allele G
may be a risk factor and people of GG genotype may be in a higher risk to develop post-traumatic osteomyelitis in
Chinese population. However, no significant link was found between rs20417 and susceptibility to post-traumatic osteomye-
litis in this Chinese cohort.
Conclusions: To our knowledge, we reported for the first time that COX-2 gene polymorphism rs689466 may contribute to
the increased susceptibility to post-traumatic osteomyelitis in Chinese population.
KEYWORDS
Post-traumatic osteomyelitis
single nucleotide polymorphism
COX-2 gene
rs20417
rs689466
case-control study
ARTICLE HISTORY
Received 14 July 2016
Revised 12 December 2016
Accepted 13 June 2017
CONTACT
B. Yu
nanfanghot@126.com;
Y.-j. Hu
huyanjun1212@163.com
Department of Orthopaedics and
Traumatology, Nanfang Hospital, No. 1838,
Guangzhou Ave. North, Baiyun District,
Guangzhou 510515, PR China
These authors contributed equally to this work.
ß2017 Society for Scandinavian Journal of Infectious Diseases
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Introduction
Cyclooxygenase (COX), also known as prostaglandin syn-
thetase (PTGS), acts as the key enzyme in the conversion
of free arachidonic acid into prostaglandins. COX partici-
pates in the regulation of inflammatory reaction proc-
esses through its products including prostaglandin E2
(PGE2), PGI2 and PGD2 [1]. COX is encoded by at least
two COX genes (COX-1 and COX-2). As one type of COX
enzymes, COX-2 plays an important role in the regula-
tion of prostanoids products, which associates with
lesion, inflammation and proliferation [2]. Human COX-2,
encoded by COX-2 gene, is located on chromosome
1q25.2-25.3, contains 10 exons, and is approximately
8.3 kb with a 4.5 kb transcript [3]. The 50flanking region
of this gene mainly participants in the regulation of
gene transcription, which contains a canonical TATA box
and several putative transcription-factor binding sites,
such as nuclear factor-jB, nuclear factor-IL-6 and a trans-
forming growth factor-bresponse element, demonstrat-
ing that a complex array of factors is involved in COX-2
gene regulation [4]. Among potential factors that affect
transcription of COX-2 gene, single nucleotide poly-
morphism (SNP) in the gene promoter is an important
aspect. The most frequently investigated functional poly-
morphisms of COX-2 gene, 765G >C (rs20417) and
1195G >A (rs689466), have been reported to be corre-
lated with several different inflammatory disorders, such
as chronic periodontitis [5,6], inflammatory bowel dis-
eases [7,8] and subclinical atherosclerosis [9]. This is
probably because these gene polymorphisms may alter
the function of COX-2 enzyme by regulation of COX-2
expression and thus, affect the synthesis of prostaglan-
dins [4,10], which involve in the pathogenesis of inflam-
matory diseases.
As a frequent type of inflammatory diseases in clinical
orthopaedics, chronic osteomyelitis (COM) is character-
ized by progressive inflammatory destruction with
new bone formation, simultaneously [11]. With respect
to disease incidence, a recent study [12] reported that
incidence of osteomyelitis in America population
between 2000 and 2009 was over twice than that
between 1969 and 1979 (24.4/100,000 vs. 11.4/100,000
person-year). Although such data were still lacking in
Chinese population, incidence of COM is in China may
be not lower than that in America, which is probably
due to the larger number of population, growing num-
ber of traffic [13] and industrial accidents in China.
Previous studies have demonstrated that healthy bone is
highly resistant to infection, which usually occurs
following large amount of inocula, severe injury and the
presence of foreign bodies. A recent study [14] indicated
that the risk of osteomyelitis following trauma and
orthopaedic surgery varied, ranging from 1% to 55%,
especially for patients with type III open fractures
(9–55%) by Gustilo–Anderson classification. The huge
digital variance implies, in addition to external factors,
host factors may also participate in the pathogenesis
of COM.
Previous studies have investigated potential roles of
host factors in the pathogenesis of COM from perspec-
tive of SNP. Osman et al. [15] reported that A allele of
rs1800871 may be risk factor for haematogenous osteo-
myelitis in Saudi Arabia. Valle-Garay et al. [16] found that
tissue plasminogen activator Alu (I/D) polymorphism may
contribute to the elevated susceptibility to bacterial
osteomyelitis in Spanish. In addition, Tsezou et al. [17]
indicated polymorphisms of interleukin-1a(IL-1a)889-
C/T, IL-4 1098-G/T and 590-C/T and IL-6 174-G/C
may increase the risk of developing COM in Greek popu-
lation. Outcomes of the above studies suggest that, as
an important aspect of host factors, SNP may involve in
the pathogenesis of COM.
Considering the above-mentioned positive relation-
ships between COX-2 gene polymorphisms and risks of
developing different inflammatory disorders as well as
the growing evidence of links between SNP and suscep-
tibility to COM, we hypothesized that COX-2 gene poly-
morphisms may be one of the pathogenetic factors of
COM. Therefore, the present study aimed to investigated
COX-2 gene polymorphisms (rs20417 and rs689466) and
susceptibility to post-traumatic osteomyelitis, one of the
most frequent COM type in Chinese population.
Materials and methods
Study design, setting, definition and population
The present study was designed as a case-control ana-
lysis. Patient group were those diagnosed with post-trau-
matic osteomyelitis in Nanfang Hospital, Guangzhou,
South China, between August 2013 and October 2015.
Post-traumatic osteomyelitis was defined as a persistent
or a long-term bone infection (at least for 10 weeks
[18,19]) following open fracture or internal fixations for
closed fracture. Diagnosis of the disease was built on
intraoperative pathological tests, or cultures from at least
two infection sites with the same organism or a definite
sinus tract connecting directly the bone. Healthy controls
were individuals without any abnormalities after thor-
ough examination in the physical examination centre of
818 L. WANG ET AL.
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our hospital. All the included participants signed the
informed consent and the current study was in accord-
ance with the tenets of Helsinki declaration. The proto-
col of the study was approved by medical ethics
committee of Nanfang Hospital, Southern Medical
University.
SNP genotyping
Ethylene diamine tetraacetic acid (EDTA) peripheral
blood samples (2 ml for each) were collected. The two
tag SNPs of the COX-2 gene (rs20417 and rs689466)
were genotyped using the Multiplex SNaPshot system
(Applied Biosystems, Foster City, CA). The detailed proce-
dures of the genotyping method were described previ-
ously [20]. The forward (F) and reverse (R) primers used
for polymerase chain reaction (PCR) and extension reac-
tions were: for rs20417: F: 50-GCCTTAAGGCATACG
TTTTGG-30,R:5
0-TACTGTTCTCCGTACCT TCAC-30, exten-
sion primer: 50-TTTTTTTTTTCCTTGTTTCTTGGAAAGAGAGG-
30. For rs689466: F: 50-TAGTATCTCACCCTCACATGC-30,R:
50-CCAAGATTATGAGTTGTG ACC-30, extension primer: 50-
CAAAAGCAAAGATGAAATTCCA-30.
Primary and secondary outcomes
Primary outcomes were comparisons for frequencies of
rs20417 and rs689466 between the two groups, includ-
ing genotype distribution, mutant allele frequency and
four genetic models (dominant, recessive, homozygous
and heterozygous models). Secondary outcomes were
clinical characteristics of post-traumatic osteomyelitis,
comparisons of clinical features and preoperative serum
levels of inflammatory cytokines [white blood cell count
(WBC), C-reactive protein (CRP), procalcitonin (PCT), inter-
leukin-6 (IL-6), tumour necrosis factor-a(TNF-a), serum
amyloid A (SAA)] among different genotypes of the two
COX-2 gene polymorphisms in the patient group.
Statistical analysis
Statistical analysis was conducted using the SPSS 17.0
software (SPSS Inc, Chicago, IL). Data distribution was
assessed for normality using the Kolmogorov–Smirnov
test. Continuous variables were revealed as the mean-
± standard deviation or median with interquartile range
(IQR) depending on data distribution. Student’st-test or
Mann–Whitney Utest was applied for normally or abnor-
mally distributed continuous variables, respectively.
Genotype frequency distributions for healthy controls
were tested for the confirmation to Hardy–Weinberg
equilibrium (HWE) using the v
2
test. The v
2
or Fisher
exact test was used to compare the frequencies of geno-
types between the two groups, with corresponding odds
ratios (ORs) and 95% confidence intervals (CIs). A pvalue
of .05 was defined as statistical significance.
Results
Baseline data between patients and healthy controls
A total of 189 patients (156 males and 33 females) with
extremity post-traumatic COM and 220 healthy controls
(167 males and 53 females) were included in the present
study finally. The gender ratio between the two groups
showed statistical difference (4.73 vs. 3.15, v
2
¼2.692,
p¼.101). However, no significant difference was also
found regarding the median age between the two
groups (patient group: 42 years, IQR: 28–50, vs. control
group: 41.5 years, IQR: 37–49, Z¼1.820, p¼.069).
Characteristics of patients diagnosed with post-
traumatic osteomyelitis
Clinical characteristics of post-traumatic osteomyelitis in
this Chinese cohort are shown in Table 1. The top three
injury types accounting for post-traumatic osteomyelitis
were traffic accident (46.01%), blunt injury (30.67%) and
falling injury (12.27%). Post-traumatic osteomyelitis was
mainly caused by open fractures (67.04%). The most fre-
quent single infection site was tibia (50.58%) and posi-
tive rate of pathogen culture was only 61.64%, with
Staphylococcus aureus (31.88%) as the most common
pathogen (Table 1).
Table 1. Clinical characteristics of post-traumatic osteomyelitis in
this Chinese cohort.
Clinical characteristics Outcomes
Top three injury type
Traffic accidents E/T (%) 75/163 (46.01)
Blunt injury E/T (%) 50/163 (30.67)
Falling injury E/T (%) 20/163 (12.27)
Open fractures E/T (%) 120/179 (67.04)
Infection side distribution left/right/bilateral 101/87/1
Infection site number single/multiple 172/17
Top three single infection site E/T (%)
Tibia 87/172 (50.58)
Femur 51/172 (29.65)
Calcaneus 12/172 (6.98)
Positive rate of pathogen culture E/T (%) 90/146 (61.64)
Pathogen for infection monomicrobial/polymicrobial 69/21
Pathogen for monomicrobial infection E/T (%)
Staphylococcus aureus 22/69 (31.88)
Pseudomonas aeruginosa 19/69 (27.54)
Staphylococcus epidermidis 5/69 (7.25)
Acinetobacter baumannii 4/69 (5.80)
Escherichia coli 4/69 (5.80)
Others 15/69 (21.73)
E/T, events/total (available data).
INFECTIOUS DISEASES 819
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Frequency of the two COX-2 gene polymorphisms in
patients and healthy controls
All genotyped SNPs were in HWE for healthy controls
(For rs20417, p
(HWE)
¼.551, for rs689466, p
(HWE)
¼.487).
As shown in Table 2, significant association was found
between rs689466 and post-traumatic osteomyelitis by
recessive model (GG vs. AA þAG) (OR ¼1.74, 95% CI:
1.098–2.755, p¼.018). Although no statistical differences
were identified of rs689466 between the two groups by
allele model (G vs. A, OR ¼1.262, 95% CI: 0.958–1.662,
p¼.098) or homozygous model (GG vs. AA, OR ¼1.612,
95% CI: 0.936–2.775, p¼.084), outcomes revealed a ten-
dency that allele G may be a risk factor and people of
GG genotype may be in a higher risk to develop post-
traumatic osteomyelitis in Chinese population. However,
no significant association was observed between COX-2
rs20417 polymorphism and the susceptibility to post-
traumatic osteomyelitis (Table 2).
Comparisons of clinical features and preoperative
serum levels of different inflammatory cytokines
among different genotypes of the COX-2 gene
polymorphisms in patient group
As revealed in Table 3, significant difference was found
regarding serum IL-6 levels among three different geno-
types of rs20417 (p¼.017). However, considering only
one patient data was available for analysis in the CC
group, we removed this group and performed further
comparisons between the GG and CG genotype groups.
Outcomes showed significantly higher serum levels of
CRP (p¼.017) and IL-6 (p¼.006) in the GG group than
those in the CG group. With respect to outcomes among
genotype groups of rs689466, in addition to the statis-
tical difference of sex ratio among the three genotype
groups (p¼.014), no significant differences were identi-
fied in another outcomes.
Discussion
Outcomes of the current study suggest that COX-2 gene
polymorphism rs689466 may contribute to the increased
susceptibility to post-traumatic osteomyelitis in Chinese
population. People with GG genotype of rs689466 poly-
morphism may be a higher risk group to develop post-
traumatic osteomyelitis.
COM is defined as pathogens or auto-inflammatory
diseases associated, a persistent or a long term bone
infections. Nowadays, COM still represents great chal-
lenges to clinicians, not only for its complex treatment
Table 2. Frequency of COX-2 gene polymorphisms (rs20417 and rs689466) in patients with post-traumatic osteomyelitis and healthy controls.
SNP site Genotype distribution no. (%) Dominant model Recessive model Allele model Homozygous model Heterozygous model
Patients Controls pValue pValue OR (95%CI) pValue OR (95%CI) pValue OR (95% CI) pValue OR (95% CI) pValue OR (95% CI)
rs20417 GG þCG vs. CC GG vs. CC þCG G vs. C GG vs. CC CG vs. CC
CC 1 (0.5) 0 (0.0) .113 p¼.462 p¼.095 p¼.076 p¼.450 p¼1.000
CG 23 (12.2) 17 (7.7) OR ¼0.995 OR ¼0.576 OR ¼0.567 OR ¼0.994 OR ¼0.958
GG 165 (87.3) 203 (92.3) 95% CI: 0.984–1.005 95% CI: 0.299–1.108 95% CI: 0.302–1.068 95% CI:0.982–1.006 95% CI: 0.882–1.042
rs689466 GG þAG vs. AA GG vs. AA þAG G vs. A GG vs. AA AG vs. AA
AA 52 (27.5) 64 (29.1) .053 p¼.724 p¼.018 p¼.098 p¼.084 p¼.606
AG 82 (43.4) 114 (51.8) OR ¼1.081 OR ¼1.740 OR ¼1.262 OR ¼1.612 OR ¼0.885
GG 55 (29.1) 42 (19.1) 95% CI: 0.702–1.665 95% CI: 1.098–2.755 95%CI: 0.958–1.662 95% CI: 0.936–2.775 95% CI: 0.557–1.407
Bold Value signifies p0.05.
SNP, single-nucleotide polymorphism; OR, odds ratio; CI, confidence interval.
820 L. WANG ET AL.
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and a higher risk of recurrence [18], but also for the sig-
nificantly increased economic cost [21] and burden, both
personally and socially. In addition, patients with COM
suffer from a higher risk of disabilities, both physically
and psychologically [22]. Moreover, outcomes of several
recent studies revealed that patients with COM may
have elevated susceptibility to other accompanying dis-
eases, such as rheumatoid arthritis [23], ischaemic stroke
[24] and diabetes mellitus [25]. COM used to be seque-
lae of acute haematogenous osteomyelitis, but has
recently increasing from post-traumatic osteomyelitis
(open fractures and closed fracture for internal fixation)
and diabetic foot osteomyelitis. The average incidence
of post-traumatic osteomyelitis is approximately 5% [26],
which is affected by both external/environmental and
internal/host factors. Currently, external factors have
been widely reported [14], however, explorations on
host factors remain quite few. In recent years, several
studies tried to investigate potential roles of host factors
for osteomyelitis from perspective of SNP, which pro-
vided new insight into the pathogenesis of COM.
As mentioned previously, COX-2 associates with
inflammation through the regulation of prostanoids
products, serum level of which may be affected by COX-
2gene polymorphisms. Currently, rs20417 and rs689466
are the most frequently reported two polymorphisms
sites of COX-2 gene. In addition to the inflammatory dis-
eases, previous studies also reported that the two gene
polymorphisms may be associated with the risk of devel-
oping another diseases, such as colorectal cancer [27],
breast cancer [28] and acute myeloid leukemia (AML)
[29]. In the present study, we found rs689466 may be
linked to the increased susceptibility to post-traumatic
osteomyelitis. In addition, outcomes of recessive model
imply that people with GG genotype of rs689466 may
be a group with a higher risk for the susceptibility to
post-traumatic osteomyelitis in Chinese population.
In order to explain potential roles of the COX-2 gene
polymorphisms in the pathogenesis of post-traumatic
osteomyelitis, we compared clinical features as well as
preoperative serum levels of six different cytokines
among different genotypes of rs20417 and rs689466.
However, in addition to the statistical differences of IL-6
levels among genotypes of rs20417 and sex ratios
among genotypes of rs689466, no significant differences
were identified in another aspect among the genotype
groups of the two sites. This may be caused by the fact
that post-traumatic osteomyelitis is injury associated dis-
ease, serum cytokines levels are affected by many exter-
nal factors apart from genetic variations, such as injury
Table 3. Comparisons of clinical characteristics among different genotypes of the COX-2 gene polymorphisms in patients with post-traumatic osteomyelitis.
Items rs20417 rs689466
GG CG CC pValue GG AG AA pValue
Age 38.8 ± 15.17 34.39 ± 14.93 26.00 .309
a
39.6 ± 13.74 35.5 ± 14.82 40.96 ± 16.62 .090
Sex ratio (M/F) 136/29 20/3 0/1 .164 43/12 75/7 38/14 .014
Positive rate of culture (%) (E/T) 62.31 (81/130) 56.25 (9/16) NA .638
a
60.46 (26/43) 64.41 (38/59) 59.09 (26/44) .845
Polymicrobial infection (%) (E/T) 24.69 (20/81) 11.11 (1/9) NA .618
a
11.54 (3/26) 31.58 (12/38) 23.08 (6/26) .177
WBC (10
9
/l) Median 7.16 6.58 6.80 .880 6.59 7.34 6.98 .266
(IQR) (5.82, 8.53) (5.73, 8.57) (6.80, 6.80) (5.35, 81.4) (6.04, 8.56) (5.79, 8.56)
CRP (mg/l) Median 6.25 2.8 8.17 .054 5.75 4.82 5.89 .424
(IQR) (2.52, 18.63) (1.69, 9.1) (8.17, 8.17) (1.84, 15.83) (1.67, 14.01) (3.57, 17.72)
PCT (ng/ml) Median 0.034 0.036 0.020 .373 0.031 0.036 0.033 .994
(IQR) (0.023, 0.051) (0.022, 0.071) (0.02, 0.02) (0.024, 0.047) (0.024, 0.048) (0.022, 0.062)
IL-6 (pg/ml) Median 17.92 7.66 46.93 .017 11.37 17.74 18.39 .373
(IQR) (8.17, 80.93) (3.07, 29.72) (46.93, 46.93) (5.08, 81.02) (8.62, 73.50) (6.97, 48.56)
TNF-a(pg/ml) Median 9.31 8.63 11.30 .443 9.67 9.14 9.42 .500
(IQR) (7.57, 12.00) (6.60, 11.77) (11.3, 11.3) (7.60, 11.15) (7.03, 11.75) (8.01, 13.80)
SAA (mg/l) Median 9.40 5.50 3.30 .504 17.60 5.95 11.90 .378
(IQR) (3.75, 29.05) (1.75, 84.05) (3.30, 3.30) (5.02, 46.60) (2.42, 19.45) (3.32, 21.27)
Bold Values signify p0.05.
IQR, interquartile range; M/F, male/female; E/T, events/total; WBC, white blood cell count; CRP, C-reactive protein; PCT, procalcitonin; IL-6, interleukin-6; TNF-a, tumour necrosis factor-a; SAA, serum amyloid A.
a
Comparisons were performed between patients with the GG and CG genotype groups of rs20417.
INFECTIOUS DISEASES 821
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type and degree, previous intervention, disease course.
Therefore, in order to eliminate influences of external
factors, the optimal patients to investigate effects of
host genetic variations on COM are those with haema-
togenous OM. However, these patients represent just
approximate 15% of all COM patients [30] and conse-
quently, large sample series of haematogenous OM
patients are quite difficult to collect.
The present study had several limitations. Firstly,
although sample size of the present study is larger than
most of the published studies on COM SNPs, it is still far
from enough to confirm the conclusions with reliability.
In addition, lopsided gender distribution between
patients and healthy controls may also affect outcomes.
Therefore, more studies with a larger sample size are
warranted. Secondly, conclusions of this study were just
built on case-control comparisons, future functional
explorations should be performed to testify that carriers
of the COX-2 gene rs689466 SNP GG genotype are more
prone to post-traumatic osteomyelitis. Furthermore,
potential mechanisms underlying these outcomes should
be conducted. Thirdly, due to the fact that post-trau-
matic osteomyelitis is a more complex inflammatory dis-
ease, more SNPs sites should be included for analysis to
better evaluate roles of genetic variations in the patho-
genesis of such injury associated infection.
In conclusion, we reported for the first time that COX-
2 gene polymorphism rs689466 may contribute to the
elevated susceptibility to post-traumatic osteomyelitis in
Chinese population. Moreover, population with GG
genotype of this site may be a group with a higher risk
to develop such disorder.
Acknowledgements
The authors thank Prof. Allen P. Liang for his contribution to
revise this paper.
Disclosure statement
The authors declare that they have no conflict of interests.
Funding
This study was supported by National Natural Science Foundation
of China (Grant No. 81572165), Guangdong Provincial Science and
Technology Department Plan Projects (Grant No.
2016B090913004), Guangzhou Science and Technology Program
key projects Plan Projects (Grant No. 201508020035) and
Presidential Foundation of Nanfang Hospital (Grant No.2014C014).
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