| Project/Area Number |
22510213
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical genome science
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| Research Institution | Tokai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
INOKO Hidetoshi 東海大学, 医学部, 教授 (10101932)
INOUE Ituro 東海大学, 医学部, 教授 (00192500)
SHIINA Takashi 東海大学, 医学部, 准教授 (00317744)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 疾患関連遺伝子 / 稀少変異 / 関節リウマチ / エクソーム解析 / 感受性遺伝子 / 稀少変異体 / 次世代シーケンサ / 希少変異体 / Long-Range PCR / Exome解析 |
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| Research Abstract |
The butyrophilin-like protein 2 gene (BTNL2) within the class III region of the Major Histocompatability Complex (MHC) genomic region was identified as a rheumatoid arthritis (RA) susceptibility gene by exome sequencing (19 RA cases) with stepwise filtering analysis and then validated by Sanger sequencing and association analysis using 432 cases and 432 controls. Logistic regression of the Sanger-sequenced single nucleotide variants (SNVs) in an association study of 432 cases and 432 controls showed that twelve non-synonymous SNPs in BTNL2 were significantly associated with RA. The lowest p values were obtained from 3 SNPs, rs41521946, rs28362677, and rs28362678, which were in absolute linkage disequilibrium: p = 4.55E-09, OR = 1.88, 95% CI = 1.52 - 2.33. The BTNL2 locates on chromosome 6 between HLA-DRB1 and NOTCH4 and is 170 kb apart from these two genes. Although DRB1 and NOTCH4 were reported to be RA-susceptible, the 3 BTNL2 SNPs retained significant association with RA when evaluated by the logistic regression with the adjustment for RA-susceptible HLA-DRB1 alleles in Japanese or rs2071282-T in NOTCH4: p = 0.0156 and p = 0.00368, respectively. These results suggest that the 3 non-synonymous SNPs in BTNL2 confer RA-risk independently from HLA-DRB1 and NOTCH4
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