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It is herein discussed what should be measured as predictors of atherosclerosis, to increase the predictive power of coronary risk evaluation in clinical practice. Plasma apolipoprotein (apo)B and apoAI have been reported to be stronger predictors of coronary artery disease (CAD) than plasma low-density lipoprotein (LDL)-cholesterol (C) and high-density lipoprotein (HDL)-C. The estimation of plasma levels of remnants of TG-rich lipoproteins is also important for coronary risk evaluation. An increase in plasma small, dense LDL is a risk factor for CAD. It is not practical to measure plasma small, dense LDL as a routine clinical examination. We should estimate the plasma levels of small, dense LDL by plasma triglyceride (TG), apoB, and HDL-C levels. Oxidized LDL (ox-LDL) plays an important role in atherosclerosis. Further large-scale, prospective studies are necessary to determine whether the measurement of plasma ox-LDL and autoantibodies against ox-LDL is an essential predictor of atherosclerosis. High plasma levels of Lp(a) are a risk factor for atherosclerotic vascular diseases in subjects with high plasma LDL-C levels and multiple coronary risk factors. Metabolic syndrome (MS) has been recognized recently as a predictor of CAD. As a result, it should be elucidated whether MS must be involved in the coronary risk evaluation score because all components of MS are involved in the score. A high plasma level of high-sensitivity C-reactive protein (hs-CRP) is an important predictor of atherosclerotic diseases. Whether it is essential to measure the plasma levels of atherosclerosis surrogate markers in clinical practice remains to be elucidated. It is concluded that plasma levels of apoB, apoAI, remnant-like particle (RLP)-C, lipoprotein (a) [Lp(a)], and hs-CRP in addition to those of lipids should be measured as predictors of atherosclerosis in clinical practice. We need to establish a new atherosclerosis risk evaluation scoring system involving the above factors, based on large-scale, prospective studies, to prevent atherosclerotic vascular diseases. In Japan, plasma levels of Lp(a), RLP-C, and hs-CRP are routinely measured in clinical practice. As a result, it would be rather easy to establish a new atherosclerosis risk evaluation scoring system in Japan.

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The butyrophilin-like protein 2 gene (BTNL2) within the class III region of the major histocompatibility complex 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 in an association study of 432 cases and 432 controls showed that 12 non-synonymous single-nucleotide polymorphisms (SNPs) in BTNL2 were significantly associated with RA. The lowest P-values were obtained from three SNPs, rs41521946, rs28362677 and rs28362678, which were in absolute linkage disequilibrium: P=4.55E-09, odds ratio=1.88, 95% confidence interval=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 three 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 three non-synonymous SNPs in BTNL2 confer RA risk independently from HLA-DRB1 and NOTCH4.