Table I. CRP SNP Rs Number, Location, Alleles, and Allele Frequency in NHANES III By

Table I. CRP SNP rs number, location, alleles, and allele frequency in NHANES III by race/ethnicity

rs number
(SeattleSNPs*) / SNP Location / Allele / White, not Hispanic
(n=2,630) / Black, not Hispanic
(n=2,108) / Mexican-American
(n=2,073) / Other
(n=348)
rs3093058
(790) / 5¢ flanking / A
T / 0.998
0.002 / 0.837
0.163 / 0.986
0.014 / 0.950
0.050
rs3091244
(1440) / 5¢ flanking / A
C
T / 0.063
0.636
0.301 / 0.273
0.444
0.283 / 0.049
0.592
0.358 / 0.108
0.609
0.283
rs1417938
(1919) / Intron 1 / A
T / 0.700
0.300 / 0.880
0.120 / 0.655
0.345 / 0.764
0.236
rs34200896
(2513) / Exon 2 / C
T / 1.00
0.00 / 1.00
0.00 / 1.00
0.00 / 1.00
0.00
rs34340208
(2612) / Exon 2 / A
G / 0.00
1.00 / 0.0002
0.9998 / 0.0002
0.9998 / 0.00
1.00
rs1800947
(2667) / Exon 2 / C
G / 0.028
0.972 / 0.0066
0.9934 / 0.02
0.98 / 0.019
0.981
rs3093066
(3006) / 3¢ UTR / A
C / 0.005
0.995 / 0.230
0.770 / 0.016
0.984 / 0.054
0.946
rs1205
(3872) / 3¢ flanking / A
G / 0.347
0.653 / 0.212
0.788 / 0.355
0.645 / 0.357
0.643
rs2808630
(5237) / 3¢ flanking / A
G / 0.714
0.286 / 0.843
0.157 / 0.789
0.211 / 0.788
0.212

*SeattleSNPs nomenclature in reference to GenBank accession number AF449713

Abbreviations: Untranslated region (UTR)

Table II. Common haplotypes (>5% frequency) inferred within each race/ethnicity

Race/ethnicity / rs3093058 / rs3091244 / rs1417938 / rs1800947 / rs3093066 / rs1205 / rs2808630 / Estimated frequency
White, not Hispanic
A / C / A / G / C / A / A / 0.31
A / T / T / G / C / G / A / 0.30
A / C / A / G / C / G / G / 0.28
A / A / A / G / C / G / A / 0.06
Black, not Hispanic
A / A / A / G / A / G / A / 0.23
A / C / A / G / C / A / A / 0.20
T / T / A / G / C / G / A / 0.17
A / C / A / G / C / G / G / 0.15
A / T / T / G / C / G / A / 0.12
A / C / A / G / C / G / A / 0.08
Mexican-American
A / T / T / G / C / G / A / 0.34
A / C / A / G / C / A / A / 0.33
A / C / A / G / C / G / G / 0.21

Other

A / C / A / G / C / A / A / 0.34
A / T / T / G / C / G / A / 0.24
A / C / A / G / C / G / G / 0.21
A / A / A / G / C / G / A / 0.05
A / A / A / G / A / G / A / 0.05
T / T / A / G / C / G / A / 0.05

Haplotypes were inferred using SAS/Genetics PROC HAPLOTYPE stratified by race/ethnicity. This table represents the most likely haplotype pair inferred for each individual and does not reflect the uncertainty of the inference.

Table III. Final model for non-CRP variables associated with C-reactive protein levels in NHANES III (R2 = 0.1915)

Variable / Beta coefficient
(95% CI) / SE / t / p-value
(Satterthwaite method)
Intercept / -2.65
(-3.51, -1.80) / 0.41 / -6.43 / <0.0001
(<0.0001)
Female / -1.16
(-1.55, -0.77) / 0.19 / -6.20 / <0.0001
Race/ethnicity
Non-Hispanic white
Non-Hispanic black
Mexican-American / .
0.13
(0.08, 0.18)
0.03
(-0.03, 0.10) / .
0.03
0.03 / .
5.12
1.10 / (<0.0001)
.
<0.0001
0.2834
Current smoker / 0.10
(0.06, 0.15) / 0.02 / 4.76 / 0.0001
(<0.0001)
Age / 0.004
(<0.01, 0.01) / 0.01 / 5.70 / <0.0001
(<0.001)
Level of education / -0.02
(-0.07, 0.02) / 0.02 / -1.03 / 0.3129
(0.3024)
Prevalent CHD / 0.3187
(0.09, 0.55) / 0.11 / 2.86 / 0.0090
(0.0044)
ln(BMI) / 0.76
(0.66, 0.85) / 0.04 / 17.04 / <0.0001
(<0.0001)
ln(total cholesterol) / -0.21
(-0.31, -0.11) / 0.05 / -4.31 / 0.0003
(<0.0001)
ln(HDL) / -0.10
(-0.21, 0.01) / 0.05 / -1.87 / 0.0744
(0.0619)
ln(triglycerides) / -0.04
(-0.09, 0.02) / 0.03 / -1.37 / 0.1829
(N/a)
ln(HbA1C) / 0.39
(0.22, 0.55) / 0.08 / 4.75 / 0.0001
(<0.0001)
Diastolic blood pressure / -0.002
(-0.01, <0.01) / 0.002 / -1.35 / 0.1895
(N/a)
Female x ln(triglycerides) / 0.24
(0.19, 0.30) / 0.03 / 9.16 / <0.0001
(<0.0001)
Female x diastolic blood pressure / 0.003
(<0.01, 0.01) / 0.002 / -1.03 / 0.3129
(0.0274)

Table IV. Association between serum C-reactive protein levels and CRP SNPs (dominant model) in NHANES III adjusting for covariates by race/ethnicity.

SNP
Genotype / Beta
(95% CI) / SE / t / p-value
White / Black / Mexican-American / White / Black / Mexican-American /

White

/ Black / Mexican-American / White / Black / Mexican-American
rs3093058
AA
AT/TT / REF
-0.05
(-0.31, 0.21) / REF
0.25
(0.15, 0.34) / REF
0.01
(-0.16, 0.18) / REF
0.13 / REF
0.05 / REF
0.08 / REF
-0.43 / REF
5.43 / REF
0.13 / REF
0.6702 / REF
<0.0001 / REF
0.8952
rs3091244 / N/a / N/a / N/a / N/a / N/a / N/a / N/a / N/a / N/a / N/a / N/a / N/a
rs1417938
AA
AT/TT / REF
0.02
(-0.03, 0.07) / REF
0.02
(-0.04, 0.08) / REF
0.01
(-0.05, 0.08) / REF
0.02 / REF
0.03 / REF
0.03 / REF
0.97 / REF
0.58 / REF
0.44 / REF
0.3424 / REF
0.5679 / REF
0.6652
rs1800947
GG
CG/CC / REF
-0.06
(-0.14, 0.02) / REF
0.03
(-0.35, 0.40) / REF
-0.12
(-0.27, 0.02) / REF
0.04 / REF
0.18 / REF
0.07 / REF
-1.54 / REF
0.15 / REF
-1.81 / REF
0.1378 / REF
0.8797 / REF
0.0826
rs3093066
CC
AC/AA / REF
0.01
(-0.18, 0.20) / REF
0.01
(-0.05, 0.08) / REF
-0.05
(-0.21, 0.10) / REF
0.09 / REF
0.03 / REF
0.07 / REF
0.09 / REF
0.43 / REF
-0.70 / REF
0.9316 / REF
0.6719 / REF
0.4924
rs1205
GG
AG/AA / REF
-0.43
(-0.10, 0.02) / REF
-0.15
(-0.24, -0.07) / REF
-0.06
(-0.12, 0.01) / REF
0.03 / REF
0.04 / REF
0.03 / REF
-1.46 / REF
-3.82 / REF
-1.89 / REF
0.1570 / REF
0.0009 / REF
0.0714
rs2808630
AA
AG/GG / REF
0.02
(-0.04, 0.08) / REF
-0.10
(-0.18, -0.03) / REF
0.01
(-0.06, 0.07) / REF
0.03 / REF
0.04 / REF
0.03 / REF
0.71 / REF
-2.87 / REF
0.20 / REF
0.4865 / REF
0.0086 / REF
0.8461

Table V. Multiple R2 for SNP models by race/ethnicity

a) General genotype model (Table 3)

SNP / White
(p-value*) / Black
(p-value*) / Mexican-American
(p-value*)
(none) / 0.1858 / 0.2039 / 0.1923
rs3093058 / 0.1859
(0.6663) / 0.2279
(<0.0001) / 0.1952
(0.8941)
rs3091244 / 0.1873
(0.4090) / 0.2274
(<0.0001) / 0.1998
(0.1069)
rs1417938 / 0.1867
(0.7126) / 0.2043
(0.7873) / 0.1977
(0.7146)
rs1800947 / 0.1915
(0.0331) / 0.2087
(0.8784) / 0.1848
(0.0690)
rs3093066 / 0.1865
(0.9309) / 0.2064
(0.7131) / 0.1921
(0.4127)
rs1205 / 0.1814
(0.1895) / 0.2173
(0.0006) / 0.2003
(0.0171)
rs2808630 / 0.1754
(0.5751) / 0.2088
(0.0081) / 0.1953
(0.9216)

b) Dominant model (Supplementary Table 3)

SNP / White
(p-value*) / Black
(p-value*) / Mexican-American
(p-value*)
(none) / 0.1858 / 0.2039 / 0.1923
rs3093058 / 0.1859
(0.6663) / 0.2279
(<0.0001) / 0.1952
(0.8941)
rs3091244 / N/a / N/a / N/a
rs1417938 / 0.1866
(0.3325) / 0.2043
(0.5624) / 0.1976
(0.6612)
rs1800947 / 0.1908
(0.1245) / 0.2087
(0.8784) / 0.1848
(0.0698)
rs3093066 / 0.1865
(0.9309) / 0.2062
(0.6680) / 0.1920
(0.4856)
rs1205 / 0.1812
(0.1438) / 0.2136
(0.0001) / 0.1978
(0.0590)
rs2808630 / 0.1753
(0.4796) / 0.2082
(0.0042) / 0.1952
(0.8444)

P-values determined using the Satterthwaite method.

Table VI. Mean CRP levels (mg/dl) by genotype, race/ethnicity, and sex.

SNP
Genotype / Mean CRP (mg/dl)
(95% lower and upper limit mean)
White / Black / Mexican-American
Male / Female / Male / Female / Male / Female
rs3093058
AA
AT
TT / 0.34
(0.30, 0.38)
0.30
(0.16, 0.44)
. / 0.42
(0.39, 0.46)
0.48
(0.26, 0.71)
. / 0.36
(0.33, 0.39)
0.47
(0.34, 0.60)
0.58
(0.33, 0.83) / 0.48
(0.43, 0.52)
0.75
(0.60, 0.90)
0.69
(0.33, 1.05) / 0.35
(0.29, 0.40)
0.31
(0.25, 0.37)
0.70
(0.70, 0.70)1 / 0.52
(0.45, 0.60)
0.47
(0.26, 0.69)
.
rs3091244
AA
CC
TT
AC
AT
CT / 0.82
(0.28, 1.37)
0.34
(0.28, 0.39)
0.37
(0.21, 0.54)
0.38
(0.16, 0.60)
0.27
(0.21, 0.34)
0.32
(0.28, 0.37) / 0.37
(0.17, 0.57)
0.38
(0.33, 0.44)
0.43
(0.28, 0.57)
0.47
(0.34, 0.60)
0.53
(0.21, 0.86)
0.45
(0.38, 0.52) / 0.38
(0.29, 0.47)
0.38
(0.27, 0.49)
0.65
(0.28, 1.03)
0.36
(0.30, 0.43)
0.43
(0.33, 0.53)
0.34
(0.30, 0.39) / 0.50
(0.33, 0.66)
0.44
(0.36, 0.52)
0.75
(0.48, 1.03)
0.46
(0.39, 0.53)
0.64
(0.53, 0.75)
0.63
(0.50, 0.76) / 0.26
(0.13, 0.39)
0.28
(0.25, 0.31)
0.35
(0.27, 0.43)
0.60
(0.17, 1.03)
0.40
(0.10, 0.71)
0.36
(0.31, 0.42) / 0.22
(0.19, 0.25)
0.47
(0.39, 0.56)
0.50
(0.44, 0.56)
0.61
(0.39, 0.83)
0.60
(0.23, 0.97)
0.56
(0.47, 0.64)
rs1417938
AA
AT
TT / 0.34
(0.28, 0.41)
0.32
(0.28, 0.36)
0.39
(0.21, 0.56) / 0.40
(0.35, 0.45)
0.45
(0.38, 0.52)
0.42
(0.28, 0.57) / 0.39
(0.35, 0.43)
0.44
(0.34, 0.55)
0.22
(0.20, 0.24) / 0.55
(0.51, 0.60)
0.54
(0.42, 0.65)
0.86
(0.32, 1.40) / 0.33
(0.26, 0.39)
0.36
(0.29, 0.43)
0.33
(0.24, 0.42) / 0.49
(0.41, 0.58)
0.56
(0.49, 0.63)
0.49
(0.37, 0.60)
rs1800947
GG
CG
CC / 0.33
(0.29, 0.37)
0.33
(0.26, 0.40)
. / 0.43
(0.39, 0.48)
0.32
(0.26, 0.38)
.* / 0.39
(0.36, 0.43)
0.40
(0.10, 0.71)
. / 0.55
(0.51, 0.60)
0.51
(0.11, 0.90)
. / 0.35
(0.30, 0.41)
0.30
(0.19, 0.41)
. / 0.54
(0.46, 0.63)
0.40
(0.23, 0.58)
.
rs3093066
CC
AC
AA / 0.33
(0.29, 0.36)
0.28
(0.20, 0.36)
. / 0.43
(0.39, 0.46)
0.45
(0.13, 0.77)
. / 0.41
(0.34, 0.47)
0.39
(0.32, 0.45)
0.36
(0.25, 0.47) / 0.57
(0.50, 0.64)
0.54
(0.48, 0.59)
0.56
(0.35, 0.77) / 0.35
(0.30, 0.40)
0.26
(0.20, 0.32)
. / 0.53
(0.45, 0.60)
0.53
(0.39, 0.67)
.*
rs1205
GG
AG
AA / 0.35
(0.27, 0.42)
0.32
(0.28, 0.36)
0.37
(0.27, 0.48) / 0.46
(0.38, 0.53)
0.42
(0.38, 0.46)
0.35
(0.26, 0.43) / 0.43
(0.38, 0.49)
0.33
(0.27, 0.38)
0.38
(0.20, 0.56) / 0.60
(0.55, 0.65)
0.51
(0.39, 0.64)
0.39
(0.29, 0.50) / 0.36
(0.28, 0.44)
0.35
(0.29, 0.42)
0.29
(0.25, 0.34) / 0.57
(0.49, 0.65)
0.52
(0.42, 0.63)
0.38
(0.27, 0.49)
rs2808630
AA
AG
GG / 0.34
(0.29, 0.38)
0.34
(0.28, 0.40)
0.29
(0.24, 0.33) / 0.39
(0.34, 0.43)
0.45
(0.36, 0.53)
0.40
(0.31, 0.49) / 0.40
(0.35, 0.45)
0.39
(0.30, 0.48)
0.33
(0.23, 0.43) / 0.60
(0.52, 0.67)
0.47
(0.42, 0.53)
0.47
(0.27, 0.67) / 0.37
(0.29, 0.46)
0.33
(0.28, 0.38)
0.29
(0.19, 0.39) / 0.52
(0.43, 0.61)
0.53
(0.44, 0.61)
0.60
(0.36, 0.84)

*Insufficient data

Table VII. Satterthwaite method p-values for association between serum CRP levels and CRP haplotypes in NHANES III by race/ethnicity

Haplotype / White / Black / Mexican-American
ACACCAA
(H11) / 0.4642 / 0.4921 / 0.2510
ACAGCAA
(H21) / REF / REF / REF
ACAGCGA
(H31) / 0.8182 / 0.3943 / 0.6958
ACAGCGG
(H41) / 0.2251 / 0.6171 / 0.1915
ATTGCGA
(H51) / 0.2330 / 0.0003 / 0.0232
TTAGCGA
(H61) / 0.2565 / <0.0001 / 0.2879
AAAGCGA
(H71) / 0.0139 / 0.0923 / 0.0056
AAAGAGA
(H81) / 0.3215 / 0.0051 / 0.5609
Other2 / 0.1350 / 0.0604 / 0.4063

Referent (REF).

P-values <0.05 are highlighted by bold italics.

1Haplotypes as defined by Carlson et al20.

2Rare haplotypes (frequency <1%) were coded in aggregate as “other.”

Table VIII. Association of CRP SNPs and prevalent CHD adjusting for covariates1.

Odds ratio
(95% confidence interval)
SNP
Genotype /

White

(n=149)2 / Black
(n=44)2 / Mexican-American
(n=42)2
rs3093058
AA
AT
TT / REF
.
. / REF
0.58
(0.23, 1.47)
3.32
(0.54, 20.30) / REF
.
.
rs3091244
AA
CC
TT
AC
AT
CT / 30.11
(3.26, 278.08)
REF
1.39
(0.57, 3.40)
1.26
(0.43, 3.69)
0.10
(0.02, 0.57)
1.18
(0.62, 2.22) / 1.75
(0.68, 4.49)
REF
1.10
(0.41, 2.46)
0.70
(0.28, 1.80)
1.28
(0.52, 3.19)
0.57
(0.17, 1.95) / .
REF
0.48
(0.10, 2.37)
0.83
(0.11, 6.33)
0.26
(0.03, 2.50)
1.54
(0.56, 4.21)
rs1417938
AA
AT
TT / REF
0.92
(0.53, 1.61)
1.30
(0.55, 3.04) / REF
1.27
(0.46, 3.49)
. / REF
1.86
(0.56, 6.21)
0.74
(0.18, 3.04)
rs1800947
GG
CG
CC / REF
0.41
(0.14, 1.22)
. / REF
.
. / REF
0.11
(0.01, 0.81)
.
rs3093066
CC
AC
AA / REF
.
. / REF
1.71
(0.77, 3.81)
2.47
(0.66, 9.24) / REF
.
.
rs1205
GG
AG
AA / REF
0.93
(0.57, 1.52)
0.76
(0.34, 1.69) / REF
0.65
(0.25, 1.69)
1.11
(0.24, 5.05) / REF
1.68
(0.85, 3.30)
0.71
(0.12, 4.26)
rs2808630
AA
AG
GG / REF
1.13
(0.64, 2.00)
0.77
(0.35, 1.69) / REF
0.54
(0.22, 1.34)
1.28
(0.24, 6.78) / REF
1.64
(0.45, 6.03)
1.14
(0.08, 15.36)

1Odds ratios adjusted for sex, age, smoking status, CRP levels, BMI, total cholesterol, HDL, triglycerides, glycosylated hemoglobin, diastolic blood pressure, level of education, sex x triglyercides, and sex x diastolic blood pressure.

2Number of participants who answered “yes” to the question “Doctor ever told you had a heart attack?”

Significant associations (p<0.05) are highlighted using bold italics.