Background Familial hypercholesterolemia (FH) is a genetic reason behind premature myocardial infarction (PMI). four mutations (LDLR c.129G C, LDLR c.1867A T, LDLRAP1 c.65G C, and LDLRAP1 c.274G A) were newly found out. The prevalence of FH diagnosed by genetic tests was 4.4%. The prevalence of definite/probable FH diagnosed by DLCN and altered DLCN requirements reached 8.0% and 23.6%, respectively, and the mutation rates AMD3100 inhibitor were 33.3% and 12.2%, respectively. The low\density lipo\proteins cholesterol (LDL\C) amounts in PMI individuals with FH had been far from objective attainment. Only 1 of the FH individuals got LDL\C 2.5 mmol/L, and non-e of these had LDL\C 1.8 mmol/L. Conclusions The prevalence of FH among Chinese individuals with PMI made an appearance fairly common. Underdiagnosis and undertreatment of FH remain a big issue, which should arouse a widespread concern. test. Count data were examined using em X /em 2 test. em P /em ? ?0.05 indicated significant difference. 3.?RESULTS 3.1. Clinical characteristics and pathogenic mutations of FH A total of 225 patients who met the inclusion criteria were enrolled in the study, including 188 males (83.6%), and 37 females (16.4%), and the average age at the first onset of MI was 46.64??7.21?years old. Ten pathogenic mutations of LDLR, APOB, PCSK9 and LDLRAP1 genes were found in 11 of 225 patients, all of which were heterozygous. Among these 11 patients, there were 8 with LDLR mutation alone, 1 with APOB mutation alone, 1 with LDLRAP1 mutation alone and 1 with both LDLR (c.129G C) and LDLRAP1 mutations (LDLRAP1 c.274G A), without PCSK9 functional mutation. Among all mutations, 6 out of 10 mutations MDC1 were classified to known AMD3100 inhibitor pathogenic mutations, and other 4 mutations were classified to putative likely pathogenic mutations, which were newly discovered (Table ?(Table11). Table 1 Pathogenic mutations of familial hypercholesterolemia in premature myocardial infarction patients thead valign=”bottom” th align=”left” valign=”bottom” rowspan=”1″ colspan=”1″ Gene /th th align=”left” valign=”bottom” rowspan=”1″ colspan=”1″ Function /th th align=”left” valign=”bottom” rowspan=”1″ colspan=”1″ cDNA position /th th align=”left” valign=”bottom” rowspan=”1″ colspan=”1″ Protein position /th th align=”left” valign=”bottom” rowspan=”1″ colspan=”1″ Significance /th th align=”left” valign=”bottom” rowspan=”1″ colspan=”1″ /th /thead LDLRMissensec.129G Cp.Lys43AsnLikely pathogenicPutativeLDLRMissensec.241C Tp.Arg81CysPathogenicKnownLDLRMissensec.292G Ap.Gly98SerPathogenicKnownLDLRMissensec.1525A Gp.Ile509GluPathogenicKnownLDLRMissensec.1691A Gp.Ala564SerPathogenicKnownLDLRMissensec.1691A Gp.Ala564SerPathogenicKnownLDLRMissensec.1867A Tp.Ile623PheLikely pathogenicPutativeLDLRMissensec.2054C Tp.Pro685LeuPathogenicKnownLDLRMissensec.2054C Tp.Pro685LeuPathogenicKnownApolipoprotein BMissensec.10579C Tp. Arg3527TrpPathogenicKnownLDLRAP1Missensec.65G Cp.Trp22SerLikely pathogenicPutativeLDLRAP1Missensec.274G Ap.Val92MetLikely pathogenicPutative Open in a separate window Abbreviations: LDLR, low\density lipoprotein receptor; LDLRAP1, low\density lipoprotein receptor adaptor protein 1. Because LDLRAP1 mutations cause ARH, 10 patients were diagnosed as FH by genetic testing, including 8 patients with LDLR mutation, 1 with APOB mutation and 1 with LDLR and LDLRAP1 mutations. The prevalence of FH diagnosed by genetic testing was 4.4%. Compared to mutation\negative patients, mutation\positive patients had more severe coronary lesions, and higher LDL\C levels (Table ?(Table22). Table 2 Clinical characteristics of AMD3100 inhibitor patients with pathogenic mutations thead valign=”bottom” th align=”left” valign=”bottom” rowspan=”1″ colspan=”1″ /th th align=”left” valign=”bottom” rowspan=”1″ colspan=”1″ Total (n?=?225) /th th align=”left” valign=”bottom” rowspan=”1″ colspan=”1″ Mutation positive (n?=?10) /th th align=”left” valign=”bottom” rowspan=”1″ colspan=”1″ Mutation negative (n?=?215) /th th align=”left” valign=”bottom” rowspan=”1″ colspan=”1″ em P /em \value /th /thead Baseline dataMale, n (%)188 (83.6)9 (90.0)179 (83.3)0.574Body mass index (kg/m2)26.71??3.5128.54??6.4026.62??3.320.09Age at the first onset of myocardial infarction (yrs)46.64??7.2144.80??6.3646.73??7.250.374Gensini score54 (34,79)70 (53110)54 (33,76)0.043Family history of premature coronary heart disease49 (21.8)2 (20.0)47 (21.9)0.889White blood cells (10*9/L)7.81(6.40,9.68)7.75(6.92,9.98)7.86 (6.30,9.50)0.794Hemoglobin (g/L)141.23??16.20143.50??13.01141.13??16.350.589Glutamic oxalacetic aminopherase (U/L)26 (19,44)39 (21,73)26 (19,44)0.227Glutamic\pyruvic transaminase (U/L)27 (18,45)22 (18,66)28 (18,44)0.939Estimated glomerular filtration rate (mL/min/1.73?m2)96.72 (82.49, 104.27)84.66 (72.81, 97.23)97.45 (84.56, 104.59)0.048Risk factorsSmoking, n (%)153 (68.0)10 (100.0)143 (66.5)0.026Hypertension, n (%)116 (51.6)1 (10.0)115 (53.5)0.000Diabetes, n (%)83 (36.9)4 (40.0)79 (36.7)0.835Hyperlipidemia, n (%)75 (33.3)5 (50.0)70 (32.6)0.253Lipid profileTotal cholesterol (mmol/L)4.01 (3.32,5.10)5.04 (4.03,5.91)3.96(3.31,5.08)0.054Triglyceride (mmol/L)1.72 (1.20,2.43)2.13 (1.14,2.54)1.71(1.20,2.42)0.717High\density lipoprotein cholesterol (mmol/L)0.92 (0.82,1.05)0.85 (0.79,0.98)0.93(0.82,1.05)0.324LDL\C (mmol/L)2.47 (1.96,3.31)3.39(2.58,4.08)2.44(1.94,3.23)0.037Untreated LDL\C (mmol/L)3.63(2.98,4.35)5.33(3.73,7.37)3.62(2.96,4.29)0.005Drug administrationAntiplatelet, n (%)139 (61.8)6 (60.0)133 (61.9)0.906Calcium channel blocker, n (%)40 (17.8)0 (0.00)40 (18.6)0.133Beta\blocker, n(%)92 (40.9)5 (50.0)87 (40.5)0.549Angiotensin\converting enzyme inhibitor/angiotensin receptor blocker, n (%)78 (34.7)1 (10.0)77 (35.8)0.094Statin, n(%)109 (48.4)6 (60.0)103 (47.9)0.454 Open in a separate window Abbreviation: LDL\C, low\density lipoprotein cholesterol. 3.2. Clinical characteristics of patients with different gene mutations Although FH cases with gene mutations generally had increased levels of LDL\C, LDL\C levels of individual instances with recognized FH mutations had been broadly diverse. Only 6 out of 10 mutation\positive individuals had LDL\C amounts above 4.9 mmol/L (190?ng/dL), and LDL\C amounts were significantly higher in carriers of LDLR mutation than in those of APOB mutation (5.72?mmol/L vs 4.93?mmol/L) (Figure ?(Figure11A). Open in another window Figure 1 LDL\C amounts (A) and Gensini ratings (B) of individuals with different gene mutations. The abscissa for peer review represents different genotypes, and the ordinate represents LDL\C amounts (A) and Gensini ratings (B) (n?=?10). APOB, apolipoprotein B; LDL\C, low\density lipoprotein cholesterol; LDLR, low\density lipoprotein receptor Coronary angiography of 10 individuals with mutation\positive FH demonstrated that there have been three lesions in 8 patients, dual\vessel disease in 1, and an individual lesion in 1. The median Gensini rating of FH individuals was 70, that was significantly greater than that of non\FH individuals. It was discovered that the median Gensini rating of individuals with LDLR mutation was greater than that of these with APOB mutation (78 vs 57), suggesting the individuals with LDLR.