Common CYP7A1 promoter polymorphism associated with risk of neuromyelitis optica.
Neuromyelitis optica (NMO) is a severe idiopathic inflammatory disease of the central nervous system primarily affecting the optic nerves and spinal cord. In this study, we generated genome-wide SNP data from NMO patients and normal controls (53 cases and 240 controls), and followed up on the association signals with samples from a larger number of inflammatory demyelinating diseases, including NMO (n=93), multiple sclerosis (MS, n=71), idiopathic recurrent transverse myelitis (IRTM, n=57), and normal controls (n=240). Statistical analyses revealed that a common promoter SNP in CYP7A1 has a protective/gene dose-dependent effect on the risk of NMO (P=0.0004). A stronger association between the variables and subsequently, a higher protective effect (lower OR) on the risk of NMO were observed among patients carrying the "G/G" genotype of rs3808607 than those with the "T/G" genotype (OR=0.38/P=0.01 vs. OR=0.12/P=0.0004, respectively). The associations which were only observed in patients with NMO suggest that there are differences in the genetic etiology of the inflammatory demyelinating diseases (NMO, classical MS, and IRTM).
Department of Neurology, National Cancer Center, Gyeonggi-do, Korea.
Ho Jin
HJ
Kim
Hyun-Young
HY
Park
Eunkyung
E
Kim
Kwang-Soo
KS
Lee
Kwang-Kuk
KK
Kim
Byung-Ok
BO
Choi
Seung Min
SM
Kim
Joon Seol
JS
Bae
Soo Ok
SO
Lee
Ji Yong
JY
Chun
Tae Joon
TJ
Park
Hyun Sub
HS
Cheong
Inho
I
Jo
Hyoung Doo
HD
Shin
D000328:Adult; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009188:Myelitis, Transverse / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009471:Neuromyelitis Optica / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D005819:Genetic Markers; D002790:Cholesterol 7-alpha-Hydroxylase