Influence of SLCO1B1 521T>C, UGT2B7 802C>T and IMPDH1 −106G>A Genetic Polymorphisms on Mycophenolic Acid Levels and Adverse Reactions in Chinese Autoimmune Disease Patients

Figures & data

Table 1 PCR Primer Sequences

SNPs	Forward Primer F	Reverse Primer R
rs3832043	5ʹ ATTTAGGAGGTTAGGAGGTCAGTG 3’	5ʹ GGGAATCTAAGCTCCTATGATACAG 3’
rs13418420	5ʹ AGAAGCCTTACCAATAACAGAAACA 3’	5ʹ TCATGAATGGGCACTGAAACTA 3’
rs7439366	5ʹ GATGTAGCTTAACCTCACAATTCTC 3’	5ʹ CATTTCCCATCTTTCTTTCAGTGTA 3’
rs4149056	5ʹ GGCTTTGCTCTTCCTTCATCT 3’	5ʹ ACAAAGGGAAAGTGATCATACAATT 3’
rs4149117	5ʹ CTCATATAGCCAAATTACCCAAGTG 3’	5ʹ GGATAATCAAAATCTTACAGGCAAA 3’
rs2278294	5ʹ GCTCTGACCACACTTCCCTTCT 3’	5ʹ GATGAAGCCCTGTTCAAACTTCT 3’

Table 2 Demographic Characteristics

Characteristics
Sex (Female, %)	104 (86.7%)
Age, years	36.61±15.42
Type of autoimmune disease
Systemic Lupus Erythematosus (SLE)	81 (67.5%)
Sjogren’s Syndrome (SS)	21 (17.5%)
Other autoimmune diseases	18 (15.0%)
MMF Dose, g/d	1.22±0.48
Course of treatment, month	14±11

Table 3 Genotype Distribution of the SNPs

SNPs		Major/Minor Allele	Major Allele Homozygotes, n (%)	Heterozygote, n (%)	Minor Allele Homozygotes, n (%)	HWE p
UGT1A9 −118(dT)9/10	rs3832043	-/T	9T (–) 4 (3.33%)	9T10T (-T) 103 (85.83%)	10T (TT) 13 (10.83%)	0.000
UGT1A9 −1818T>C	rs13418420	T/C	TT 33 (27.50%)	CT 64 (53.33%)	CC 23 (19.17%)	0.417
UGT2B7 802C>T	rs7439366	C/T	CC 55 (45.83%)	CT 46 (38.33%)	TT 15 (19.83%)	0.084
SLCO1B1 521T>C	rs4149056	T/C	TT 91 (75.83%)	CT 22 (18.33%)	CC 7 (5.83%)	0.002
SLCO1B3 334T>G	rs4149117	G/T	GG 63 (52.07%)	GT 4 (3.31%)	TT 54 (44.63%)	0.000
IMPDH1 −106G>A	rs2278294	C/T	CC 24 (20.00%)	TC 60 (50.00%)	TT 36 (30.00%)	0.912

Table 4 MPA C₀/d of Different Genotypes for Each SNP

SNPs		MPA C0/d, ug/mL			p
		Major Allele Homozygotes	Heterozygote	Minor Allele Homozygotes
UGT1A9 −118(dT)9/10	rs3832043	9T 0.93 (0.11,-)	9T10T 1.45 (0.61,3.27)	10T 1.13 (0.54,1.96)	0.640
UGT1A9 −1818T>C	rs13418420	TT 1.16 (0.59,2.66)	CT 1.43 (0.65,2.26)	CC 1.45 (0.24,4.01)	0.888
UGT2B7 802C>T	rs7439366	CC 1.37 (0.66,2.16)	CT 1.80 (0.51,3.81)	TT 1.00 (0.58,2.12)	0.412
SLCO1B1 521T>C	rs4149056	TT 1.44 (0.56,2.58)	CT 0.90 (0.60,1.53)	CC 4.01 (2.48,7.24)	0.003*
SLCO1B3 334T>G	rs4149117	GG 1.42 (0.63,2.26)	GT 0.73 (0.70,-)	TT 1.45 (0.50,3.49)	0.953
IMPDH1 −106G>A	rs2278294	CC 1.43 (0.52,2.96)	TC 1.52 (0.56,3.30)	TT 1.29 (0.71,2.58)	0.943

Note: *p<0.05.

Figure 1 MPA C₀/d values of different genotypes for SLCO1B1 521T>C. MPA concentration (C0/d, ug/mL). TT CT CC: genotype of SLCO1B1 521 T>c.

Table 5 Occurrence of Adverse Reactions

Types of ADRs	n, (%)
Gastrointestinal Side Effects	33 (28.2%)
Infections	45 (38.5%)
Bacterial Infection	38 (32.5%)
Viral Infection	7 (6%)
Pneumocystis Carinii Pneumonia Infection	9 (7.7%)
Adverse Reaction of Hematologic System	44 (37.6%)
Leukopenia	17 (14.5%)
Anemia	24 (20.5%)
Decreased Platelet Count	18 (15.4%)

Table 6 Correlation of SNPs and Adverse Reactions of Different Genotypes

Type of Adverse Reaction	SNPs	Without ADRs	With ADRs	p
Infection	rs2278294	CC 20 (83.3%)	CC 4 (16.7%)	0.006*
		TC 29 (48.3%)	TC 31 (51.7%)
		TT 25 (69.4%)	TT 11 (30.6%)
Pneumocystis Carinii Pneumonia Infection	rs7439366	CC 53 (96.4%)	CC 2 (3.6%)	0.036*
		CT 39 (84.8%)	CT 7 (15.2%)
		TT 19 (100.0%)	TT 0 (0.0%)
Anemia	rs4149056	TT 75 (82.4%)	TT 16 (17.6%)	0.029*
		CT 19 (86.4%)	CT 3 (13.6%)
		CC 3 (42.9%)	CC 4 (57.1%)

Note: *p<0.05.