TY - JOUR
T1 - Gender differences in the IL6 -174G>C and ESR2 1730G>A polymorphisms and the risk of Parkinson's disease
AU - San Luciano, M.
AU - Ozelius, L.
AU - Lipton, R. B.
AU - Raymond, D.
AU - Bressman, S. B.
AU - Saunders-Pullman, R.
N1 - Funding Information:
We are indebted to our subjects for participating in the study. Dr. San Luciano was supported by an American Academy of Neurology Foundation Clinical Research Training Fellowship. Dr. Saunders-Pullman was supported by the Pfizer Society for Women's Health Research Scholar Grant for Faculty Development in Women's Health. This study was supported by grants number K23NS047256 and K02NS073836 from the NINDS (RSP), the Thomas Hartman Foundation for Parkinson's Research (RSP). The Einstein Aging Study is funded by the NIA ( AG03949 , Principal Investigator: R.B. Lipton). This publication was made possible by the CTSA Grant UL1 RR025750 and KL2 RR025749 and TL1 RR025748 from the National Center for Research Resources (NCRR) , a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research.
PY - 2012/1/11
Y1 - 2012/1/11
N2 - The -174G>C (rs1800795) single nucleotide polymorphism (SNP) in the promoter of the interleukin-6 (IL6) gene and the 1730G>A (rs4986938) SNP in the estrogen receptor beta (ESR2) may influence the risk of Parkinson's disease (PD). We investigated these SNPs in 380 unrelated US Caucasian PD cases and 522 controls, including 452 individuals of Ashkenazi Jewish (AJ) origin (260 PD, 192 controls). The G allele of the -174G>C SNP was more common in AJ PD cases (p= 0.033) as well as in Non-Jewish (NJ) men with PD (p= 0.022). The GG genotype increased the risk of PD by over two fold in NJ men (OR = 2.11, 95%CI: 1.14-3.89, p= 0.017), and approached significance in the total AJ group with PD (OR = 1.42, 95%CI: 0.97-2.06, p= 0.067). The A allele of the ESR2 1730G>A SNP was associated with a decreased risk for PD in AJ women, and in this group, having the AA genotype decreased the risk of PD by half (OR = 0.45, 95%CI: 0.22-0.92, p= 0.029). Our data supports a role for the IL6 -174G>C G allele in AJ individuals overall. In NJ Caucasians, this role appears to be gender mediated. In both groups, the effect is independent from ESR2 1730G>A. A separate association for the ESR2 1730G>A SNP was found exclusively in women of AJ descent. Other polymorphisms in tight linkage disequilibrium with the SNP differentially influencing expression, ethnic differences in allele distribution, and gender differences in genetic load related to PD, may underlie our findings. Larger studies in diverse populations, including analysis of surrounding regions are recommended.
AB - The -174G>C (rs1800795) single nucleotide polymorphism (SNP) in the promoter of the interleukin-6 (IL6) gene and the 1730G>A (rs4986938) SNP in the estrogen receptor beta (ESR2) may influence the risk of Parkinson's disease (PD). We investigated these SNPs in 380 unrelated US Caucasian PD cases and 522 controls, including 452 individuals of Ashkenazi Jewish (AJ) origin (260 PD, 192 controls). The G allele of the -174G>C SNP was more common in AJ PD cases (p= 0.033) as well as in Non-Jewish (NJ) men with PD (p= 0.022). The GG genotype increased the risk of PD by over two fold in NJ men (OR = 2.11, 95%CI: 1.14-3.89, p= 0.017), and approached significance in the total AJ group with PD (OR = 1.42, 95%CI: 0.97-2.06, p= 0.067). The A allele of the ESR2 1730G>A SNP was associated with a decreased risk for PD in AJ women, and in this group, having the AA genotype decreased the risk of PD by half (OR = 0.45, 95%CI: 0.22-0.92, p= 0.029). Our data supports a role for the IL6 -174G>C G allele in AJ individuals overall. In NJ Caucasians, this role appears to be gender mediated. In both groups, the effect is independent from ESR2 1730G>A. A separate association for the ESR2 1730G>A SNP was found exclusively in women of AJ descent. Other polymorphisms in tight linkage disequilibrium with the SNP differentially influencing expression, ethnic differences in allele distribution, and gender differences in genetic load related to PD, may underlie our findings. Larger studies in diverse populations, including analysis of surrounding regions are recommended.
KW - Estrogen receptor
KW - Gender
KW - Inflammation
KW - Interleukin 6
KW - Parkinson's disease
KW - Polymorphism
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U2 - 10.1016/j.neulet.2011.11.032
DO - 10.1016/j.neulet.2011.11.032
M3 - Article
C2 - 22155094
AN - SCOPUS:84655169613
SN - 0304-3940
VL - 506
SP - 312
EP - 316
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -