Result
Characteristics of the study population
The baseline characteristics of the subjects were shown in Table A1. There were 1993 cases in the MS group and 1079 cases in the control group. The sex and age of the control group and the MS group could be matched. During the 5-year follow-up, 325 subjects were lost to follow-up, 1615 patients in the MS group and 1039 patients in the control group were completed. (Fig. 1).
Genotype analysis was performed on NC_000007.14:g.139985896C>T of the 3072 samples. Finally, there were 1991 cases in the MS group and 1076 cases in the control group completed. The frequency distribution of NC_000007.14:g.139985896C>T genotypes and alleles in control group and MS group was basically consistent with that in HAPMAP-CHB, the frequency distribution of NC_000007.14:g.139985896C>T in both groups did not deviate from Hardy-Weinberg equilibrium. Table A2 presents the genotype and allele frequencies of the NC_000007.14:g.139985896C>T in the MS group and controls, there were no significant difference in the NC_000007.14:g.139985896C>T genotype or the allele distributions between MS and controls (P > 0.05). The comparison of baseline clinical characteristics between different genotypes in the control group and the MS group showed that there was no significant difference in clinical indicators between different genotypes in the MS group (all P > 0.05). But significant difference was observed in the control group, compared with CC genotype carriers, the CT genotype carriers had significantly higher low-density lipoprotein cholesterol (LDL-C) (P <0.05). (Table 1).
Relevance of SNP and Components of MS
The components of MS include TG, blood pressure, fasting plasma glucose (FPG), abdominal obesity, HDL-C, the relationship between the NC_000007.14:g.139985896C>T genotypes and the components were analyzed (Table 2). The results showed that there was no significant difference between the groups according to TG, blood pressure, FPG, and abdominal obesity. (all P > 0.05). It suggested that there was no association between genotypes and these components. But in group of HDL-C, significant differences were observed in the distributions of the CC genotype and the C allele of NC_000007.14:g.139985896C>T between normal HDL-C group and abnormal HDL-C group (P = 0.023 & P = 0.018, respectively). The HDL-C abnormality of the C allele is significantly higher than the T allele carriers (P < 0.05).
Relevance of SNP andendpoints of MS
The relationship between the NC_000007.14:g.139985896C>T genotypes and the endpoints were analyzed of the whole population, MS group and controls. The results showed that there was no significant difference between all-cause death, coronary heart disease, myocardial infarction, new-onset diabetes, new-onset hypertension and new-onset MS in the whole population and MS group (P > 0.05), but significant differences were observed in ischemic stroke and the genotypes of NC_000007.14:g.139985896C>T (all P < 0.05), especially in the MS group (Table 3). The incidence of ischemic stroke was significantly higher in G allele carriers than in C allele carriers (all P < 0.05). In the control group, no endpoint was associated with this locus (all P > 0.05).
Risk factors of the onset of ischemic stroke
The Logistic regression analysis was performed for screening the risk factors of the onset of ischemic stroke (Table 4). The results showed that, in the whole population, C allele and gender was the protective factors of the onset of ischemic stroke, the risk of ischemic stroke was decreased when the individual was women or with C allele. SBP was the risk factor for the onset of ischemic stroke, the risk of ischemic stroke was increased when the SBP was higher; in the MS population, C allele and gender was the protective factors of the onset of ischemic stroke, the risk of ischemic stroke was decreased when the individual was women or with C allele. The interaction effects between C allele and the components of MS on the onset of ischemic stroke showed that, in the whole population, there were negative interactions between C allele and WC, SBP, DBP, TG, HDL-C and FPG; in the MS group, there were also negative interactions between C allele and WC, SBP, DBP, TG, HDL-C and FPG. In the case of same WC, SBP, DBP, TG, HDL-C and FPG, the onset of ischemic stroke of C allele carrier were reduced (Table 5).