European versus Asian differences for the associations
between paraoxonase-1 genetic polymorphisms and
susceptibility to type 2 diabetes mellitus
, Huan Ren
c, d, #
, Mou-Ze Liu
, Ping-Fei Fang
, Da-Xiong Xiang
Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China
Received: August 1, 2017; Accepted: October 12, 2017
Many studies have examined the associations between paraoxonase-1 (PON1) genetic polymorphisms (Q192R, rs662 and L55M, rs854560)
and the susceptibility to type 2 diabetes mellitus (T2DM) across different ethnic populations. However, the evidence for the associations
remains inconclusive. In this study, we performed a meta-analysis to clarify the association of the two PON1 variants with T2DM risk. We car-
ried out a systematic search of PubMed, Embase, CNKI and Wanfang databases for studies published before June 2017. The pooled odds ratios
(ORs) for the association and their corresponding 95% conﬁdence intervals (CIs) were calculated by a random- or ﬁxed-effect model. A total of
50 eligible studies, including 34 and 16 studies were identiﬁed for the PON1 Q192R (rs662) and L55M (rs854560) polymorphism, respectively.
As for the PON1 Q192R polymorphism, the 192R allele was a susceptible factor of T2DM in the South or East Asian population (OR > 1,
P < 0.05) but represented a protective factor of T2DM in European population (OR = 0.66, 95% CI = 0.45–0.98) under a heterozygous genetic
model. With regard to the PON1 L55M polymorphism, signiﬁcant protective effects of the 55M allele on T2DM under the heterozygous
(OR = 0.77, 95% CI = 0.61–0.97) and dominant (OR = 0.80, 95% CI = 0.65–0.99) genetic models were found in the European population,
while no signiﬁcant associations in the Asian populations under all genetic models (P > 0.05). In summary, by a comprehensive meta-analysis,
our results ﬁrmly indicated that distinct effects of PON1 genetic polymorphisms existed in the risk of T2DM across different ethnic back-
type 2 diabetes mellitus
The rise of diabetes prevalence poses one of the important challenges
to global health. It is estimated that approximately 422 million adults
were diagnosed with the disease in 2014 worldwide . Diabetes is
one of the main causes of cardiovascular disease, blindness and kid-
ney failure and is the sixth leading driver of disability . Therefore,
the prevention and control of diabetes are growing up to be an ever-
increasing global health priority . Type 2 diabetes mellitus (T2DM)
comprises the majority of cases of diabetes around the world. T2DM
is a metabolic disorder of multifactorial aetiology involving many
environmental factors and genetic variants [4,5].
Human paraoxonase-1 (PON1) is a calcium-dependent 45-kD glyco-
protein composed of 355 amino acids. The esterase is synthesized
mainly by the liver and secreted into the circulation where it associates
with high-density lipoprotein (HDL) and assists in the antioxidant effect
of preventing oxidation of low-density lipoprotein (LDL). PON1 in human
beings is encoded by the PON1 genewhichmapstothelongarmof
chromosome 7 (q21-22). It has been observed that serum PON1 activity
has an important role in susceptibility and progression of T2DM [6,7].
Single nucleotide polymorphisms (SNPs) in the PON1 gene can sig-
niﬁcantly account for the catalytic ability of the enzyme. A missense
SNP at position 192 (glycine (Q) to arginine (R) substitution) (rs662) is
an important determinant of the PON1 activity . Although the R-
alloenzyme is more active towards some substrates, for example para-
oxon, other substrates such as diazoxon and sarin are hydrolysed more
rapidly by the Q-alloenzyme . In addition, the PON1 Q192R
#These authors contributed equally to this work.
*Correspondence to: Jian-Quan Luo
ª 2018 The Authors.
Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use,
distribution and reproduction in any medium, provided the original work is properly cited.
J. Cell. Mol. Med. Vol 22, No 3, 2018 pp. 1720-1732