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636 Susceptible and Prognostic Genetic Factors Associated
with Diabetic Peripheral Neuropathy: A Literature Review

CONCLUSION
Although targeted gene sequencing is still a method of choice to identify rare functional mutations in mono-
genic disorders, exome sequencing becomes an attractive and cost-effective alternative when other disease
mapping strategies provide few or ambiguous results. This review has attempted to identify the common
susceptibility and prognostic genetic factors associated with DPN in T2D (Table 1). Knowledge about these
factors is vital as DPN is one of the debilitating complications associated with T2D and identification of the
common genetic variants would be valuable for the future development of gene panels targeted for the early
detection and prognosis of DPN. Together with these gene panels, further gene expression studies will need
to be conducted to modulate effective targeted therapies for DPN in these patients.

Gene Chromosomal location Variants Associated risk/Remarks Ref.
Advanced Glycation End Receptor 6p21.32 rs1800624 Higher risk/ Defective inflammatory [23]
(AGER) pathways
Peroxisome proliferator activated 3p25.2 rs1801282 Higher risk/ Defective inflammatory [28]
receptor alpha (PPARA) pathways
Bradykinin receptor B2 (BDKRB2) 14q32.2 rs1799722 Higher risk/ Defective inflammatory [30]
pathways/African-Americans
Potassium voltage-gated channel 11p15.1 E23K, G>A rs5219 Higher risk/Chinese population/ [24]
subfamily J member 11 (KCNJ11) Altered signaling pathways
CDK5 regulatory subunit associat- 6p22.3 rs7756992 Higher risk/Chinese population [24]
ed protein 1 like 1 (CDKAL1)
Transcription factor 7 like 2 10q25.2-q25.3 rs7903146 Higher risk/Chinese population [24]
(TCF7L2)
Methylenetetrahydro folate reduc- 1p36.22 C677T r Higher risk/ Altered folate metab- [25]
tase (MTHFR) s1801133 olism
Apolipoprotein E (APOE) 19q13.32 4 allele - rs429358 - rs7412 Higher risk/ Altered lipid metabolism [26]
Adrenoceptor alpha 2B ( 2q11.2 12Glu9 rs879255577 Higher risk/Defects in regulation [27]
ADRA2B) of neurotransmitter release from
sympathetic nerves
Gene Chromosomal location Variants Associated risk/Remarks
microRNA 146a (MIR146a) 5q33.3 rs2910164 (G>C) Lower risk [50]
microRNA128a (MIR128a) 2q21.3 rs11888095 (C>T) Higher risk [50]
High mobility group box 1 8q23.1 rs6986153 Males/Higher risk [40]
pseudogene 46 (HMGB1P46)
Zinc finger and SCAN domain 1p35.1 rs71647933 Females/Higher risk [40]
containing 20 (ZSCAN20)
Serpin family E member 1 (SER- 7q22.1 rs1799768 Progressive type of DPN [41]
PINE1)
Nerve growth factor receptor 17q21.33 rs734194 Progressive type of DPN [44]
(NGFR)
Angiotensin-converting enzyme 17q23.3 rs1799752 Japanese population [46]
(ACE) diallelic polymorphism: Lower risk
Presence/absence of 287bp Higher risk
in intron 16
Heterozygous D/I
Homozygous D/D
Aldo-keto reductase family 1 mem- 7q33 rs5053 Higher risk / [48]
ber B (AKR1B1) rs759853 Altered glucose metabolism

GCDC 2017