中国苏州地区汉族人群MCP-1基因多态性与急性胰腺炎相关性研究

目的探讨中国苏州地区汉族人群单核细胞趋化因子蛋白-1(monocyte chemoattractant protein-1,MCP-1)基因-2518A/G多态性与急性胰腺炎的相关性。方法采用聚合酶链反应-限制性片段长度多态性方法检测中国苏州汉族人群急性胰腺炎(acute pancreatitis,AP)患者101例[其中包括轻症急性胰腺炎(mildAP,MAP)78例,重症急性胰腺炎(servere AP,SAP)23例]和120名健康对照的MCP-1基因-2518位点基因型分布及基因频率,并评价基因多态性与AP易感性之间的相关性。结果对照组MCP-1-2518A/G位点的AA基因型频率较SAP组和MAP组高,差异有统计学意义(P<0.01),携AG及GG基因型者患MAP的风险度约是AA基因型的5.896倍(P<0.01,OR=5.896),患SAP的风险度约为7.011倍(P<0.05,OR=7.011)。而在MAP与SAP组间AA基因型频率差异无统计学意义(P=0.997)。对照组G等位基因频率明显低于MAP(P<0.01,OR=0.318)和SAP组(P<0.01,OR=0.309)。但G等位基因频率在MAP与SAP组间基因型分布差异无统计学意义(P=0.623,OR=1.211)。结论中国苏州地区汉族人群MCP-1-2518位点AA基因型可能有助于保护机体避免发生AP,G等位基因频率较高的人可能易患AP。但AA基因型和G等位基因频率不能预测SAP的发生。     

GALNT2 rs4846914多态性位点在中国汉族人群分布及其对血脂的影响

目的 研究多肽N-乙酰半乳糖胺基转移酶2(N-acetylgalactosaminyltransferase 2,GALNT2)基因rs4846914位点在中国汉族人群中的分布频率,分析该位点对血脂水平和血脂异常的影响.方法 采用横断面调查方法,收集2397例(其中男性1511例,女性886例)汉族人群样本.采用MALDI-TOF MS技术检测rs4846914位点基因分型,采用多重线性回归法分析基因型对4项血脂指标影响程度的大小,二分类Logistic回归法分析基因型对血脂异常发病风险的大小,以P＜0.05为有统计学意义.结果 GALNT2 rs4846914位点A等位基因在中国汉族人群中的频率为20.4％.AA基因型人群的高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)水平显著高于GG基因型(P=0.034),女性人群AA基因型的总胆固醇(total cholesterol,TC)水平也显著高于GG型(P=0.019).在男性人群,AA基因型的低HDL-C血症发病风险是GG基因型的0.478倍.(P=0.045,OR=0.478,95％ CI:0.233-0.983).结论 中国汉族人群rs4846914位点以G等位基因为主,明显不同于西方人群以A等位基因为主的特点.中国汉族人群中,该位点AA基因型可增加血浆HDL-C水平,并减少男性低HDL-C血症发生.     

云南地区汉族人群PSMB8、PSMB9及TAP2基因多态性与类风湿关节炎的关联研究

目的 研究云南汉族人群中PSMB8、PSMB9及TAP2基因多态性与类风湿关节炎(rheumatoid arthritis,RA)的相关性.方法 应用聚合酶链反应-限制性片段长度多态性法对177例RA患者及288名健康对照PSMB8基因的rs2071543、rs55745125、rs138635403位点和PSMB9基因的rs17587多态性位点进行基因分型,应用多聚酶链反应扩增阻碍系统法对TAP2基因的rs2228396多态性位点进行基因分型.计算基因型及等位基因频率.采用Epi Info 7软件计算上述多态位点在RA组及正常对照组之间的比值比(OR值).结果 rs138635403及rs17587位点的等位基因及基因型频率在RA组和对照组间差异有统计学意义(P＜0.05),其中RA组rs17587的GG基因型频率(0.672)高于对照组(0.524)(OR=1.862,95％CI:1.261～2.749).结论 云南汉族人群PSMB9基因的rs17587位点多态性与RA存在关联.     

内蒙古包头地区汉族人群TNF-α-308位点基因多态性与IgA肾病的相关性研究

目的：了解内蒙古包头地区汉族人群IgA肾病患者肿瘤坏死因子α（TNF-α）-308位点基因型的分布特点。方法：应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测97例IgA肾病患者和73例正常人的TNF-α基因型。结果：IgA肾病患者组中TNF-α基因G/A多态GG、GA、AA基因型频率分别为85.6%、11.3%和3.1%,其中G和A等位基因频率分别为91.2%和8.8%。正常对照组中,TNF-α基因G/A多态GG、GA、AA基因型频率分别为91.8%、5.5%和2.7%,其中G和A等位基因频率分别为94.5%和5.5%。IgA肾病患者组与正常对照组比较,基因型频率差异有显著性（χ^2=27.2,P〈0.05）,等位基因频率之间差异无显著性（χ^2=0.659,P〉0.05）。结论：TNF-α-308位点基因多态性与内蒙古包头地区汉族人群IgA肾病的发病有相关性,等位基因频率之间差异无显著性（χ^2=0.659,P〉0.05）。     

MCP-1启动子-2518位点基因多态性与云南汉族SLE的研究

目的研究单核细胞趋化蛋白-1（MCP-1）启动子-2518位点基因多态性与云南汉族系统性红斑狼疮（SLE）及狼疮性肾炎（LN）的联系。方法采用聚合酶链反应（PCR）与限制性片段长度多态性（RFLP）方法对61例SLE患者（SLE合并LN患者28例,SLE未合并LN患者33例）和65例正常对照的MCP-1启动子-2518位点基因多态性分布进行分型,以SPSS12．0分析软件分析该基因位点多态性情况。结果各组MCP-1启动子-2518位点基因型A／G较A／A、G／G出现的频率升高;各组MCP-1启动子A／A、G／G及A／G出现的频率无显著性差异（P〉0．05）。结论MCP-1启动子-2518位点基因多态性与SLE、LN的发病和病情之间均无联系。     

广西壮族及汉族人群CD40配体基因rs3092923G/A和rs3092929A/C遗传多态性的研究

目的探讨CD40配体基因rs3092923G/A和rs3092929A/C多态性位点在广西壮族及汉族人群中的分布,同时比较其基因型及等位基因频率分布在不同种族人群之间以及同一种族不同性别之间存在的差异。方法采用单碱基延伸PCR的检测方法,分析201名广西汉族人和199名广西壮族人的CD40配体基因rs3092923G/A和rs3092929A/C多态性。结果在广西壮族人群中,CD40配体基因rs3092923G/A位点AA、AG与GG基因型频率和rs3092929A/C位点AA、AC与CC基因型频率均为86.4%、7.5%和6.0%,rs3092923G/A位点的A、G等位基因频率和rs3092929A/C位点的A、C等位基因频率均为90.2%、9.8%;在广西汉族人群中,CD40配体基因rs3092923G/A位点AA、AG与GG基因型频率和rs3092929A/C位点AA、AC与CC基因型频率均为93.0%、4.0%、3.0%,rs3092923G/A位点的A、G等位基因频率和rs3092929A/C位点的A、C等位基因频率均为95.0%、5.0%。将这2个多态性位点基因型分布频率在2个民族人群中比较,差异均无显著性(P均>0.05),而等位基因频率却有着显著性差异(P均<0.05)。另外,将这2个位点多态性分布频率在男女性别之间作比较,差异都没有显著性(P均>0.05)。进一步与人类基因组计划公布的4个人群相比,广西汉族人群的rs3092923G/A和rs3092929A/C 2位点基因型和等位基因频率与非洲、日本、欧洲和北京人群比较,差异都具有显著性(P均<0.05)。结论在广西地区壮族及汉族人群中存在着CD40配体基因多态性。广西汉族人群CD40配体基因多态性的分布频率同其他种族人群比较存在着显著性差异,这种差异可能是导致与CD40配体相关的疾病在不同种族人群间的临床表现以及发病率存在明显不同的原因之一。     

广东地区汉族人群的hGSTP1Ile105Val基因多态性的研究

目的:对广东地区汉族人群的hGSTP1Ile105Val基因多态性进行研究。方法:应用PCR-RFLP(基因体外扩增限制性片段长度多态性分析)的技术方法进行研究。结果:该人群中GSTP1基因在105位点的野生型纯合子(AA)基因型的分布频率为57.4%,突变型纯合子(GG)基因型为6.7%,杂合子(AG)基因型为35.9%。结论:GSTP1纯合突变基因型在广东地区汉族人群中的分布频率为6.7%。     

ECE-1基因多态性与原发性高血压的相关性

目的探讨内皮素转换酶-1(endothelin converting enzyme-1,ECE-1)基因多态性与中国北方汉族人群原发性高血压的相关性。方法采用病例-对照方法,在中国北方汉族人群中收集178例原发性高血压患者和194例健康对照者,应用聚合酶链式反应-连接酶检测方法测定ECE-1基因C-338A和T-839G位点的多态性。结果在原发性高血压组中,C-338A位点CA+AA基因型和A等位基因分布频率显著高于对照组(P=0.006;P=0.014);T-839G位点基因型和等位基因分布频率无显著差异。结论 ECE-1基因C-338A位点多态性与中国北方汉族人群原发性高血压的发病具有一定相关性。     

瘦素受体基因Lys109Arg多态性与温州地区高血压合并肥胖的相关性研究

目的了解温州地区汉族人群瘦素受体Lys109Arg基因型分布;探讨该基因多态性与高血压合并肥胖的关系。方法运用序列特异性引物-聚合酶链式反应技术(PCR-SSP)测定无亲缘关系的381例温州地区汉族人群的瘦素受体基因Lys109Arg多态性(正常对照组111例,高血压病合并肥胖148例,高血压病非肥胖122例)。结果高血压合并肥胖组瘦素受体基因Lys109Arg的AA、AG和GG基因型频率分别为0.020、0.135和0.845,等位基因A和G频率分别为0.088和0.912;高血压合并非肥胖组基因型频率分别为0.049、0.246和0.705,基因型A和G等位基因频率分别为0.172和0.828;正常对照组基因型表达频率分别为0.027、0.315和0.658,A和G等位基因频率分别为0.185和0.815;Lys109Arg位点多态性的分布频率在对照组和病例组间差异有统计学意义(χ2=7.688,P0.05),且G等位基因频率在高血压合并肥胖患者中显著高于非肥胖组(χ2=8.634,P0.05)。结论瘦素受体基因Lys109Arg多态性与温州地区汉族人群高血压合并肥胖相关。     

基质金属蛋白酶-3基因多态性与脑卒中亚型的相关性

目的 探讨中国北方汉族人群基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)基因多态性与缺血性脑卒中(ischemic stroke,IS)亚型的相关性.方法 应用病例对照研究,选取289例急性缺血性脑卒中患者(发病≤3d)和175名同期健康体检者.卒中组按急性卒中治疗低分子肝素试验病因分型法分为大动脉粥样硬化性(large artery atherosclerotic,LAA)脑卒中185例,小动脉闭塞性(small artery occlusion,SAO)脑卒中104例.选取MMP-3基因rs3025058(-11715A/6A),rs522616(-709A/G)及rs679620(133A/G)3个常见单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点,应用聚合酶链反应限制性片段长度多态性或直接测序法对MMP-3基因3个SNP位点进行基因分型.结果 3个位点存在不完全连锁不平衡,且基因多态性均与LAA型脑卒中相关(P＜0.05).在显性模型中,rs3025058位点5A5A+5A6A基因型携带者患LAA型脑卒中的风险是6A6A基因型携带者的1.72倍(P=0.017,OR=1.72,95％CI:1.10～2.69);rs522616位点GG+ AG基因型携带者患LAA型脑卒中的风险是AA基因型携带者的0.52倍(P=0.005,OR=0.52,95％CI:0.33～0.82);rs679620位点AA+ GA基因型携带者患LAA型脑卒中的风险是AA基因型携带者的1.55倍(P=0.042,OR=1.55,95％CI:1.01～2.37).但是,3个SNPs基因型和等位基因频率在对照组与SAO型脑卒中之间差异无统计学意义(P＞0.05).另外,LAA组5A-A-A及6A-A-A单倍型高于对照组,差异有统计学意义(P＜0.05),而6A-G-G单倍型显著低于对照组(P＜0.01).结论 MMP-3血清水平在LAA型脑卒中急性期增高明显,SAO型脑卒中次之;中国北方汉族人群MMP-3基因rs3025058,rs522616及rs679620多态性可能与LAA型脑卒中易感性相关.     

A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with psoriasis

Psoriasis is one of the most common inflammatory diseases of skin. MCP-1 is an important CC-type chemokine responsible for monocytes and T lymphocytes recruitment in inflammatory conditions. A single nucleotide polymorphism of the MCP-1 gene in the gene regulatory region was found to be related to the expression of MCP-1, and the associations of this polymorphism with many inflammatory diseases were conformed. However, the significance of this polymorphism in psoriasis remains unclear. Therefore, we examined this polymorphism in 507 patients with plaque-type psoriasis and 530 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method. We also tested the serum MCP-1 in 320 patients and 160 controls and compared the serum MCP-1 level in patients of different genotypes. Our results showed that the frequency distribution of the AA, AG and GG genotypes between the patients and the controls was statistically different (P = 0.031); significantly increased risk for psoriasis was associated with the AG, GG and AG + GG genotype. The frequency distribution of the AA, AG and GG genotypes was also different between female psoriasis patients and controls (P = 0.025), between type I psoriasis patients and controls (P = 0.025), between psoriasis patients without positive familial history and controls (P = 0.048), and between patients with psoriasis area and severity index of > or = 10 and controls (P = 0.041). MCP-1 serum level was significantly higher in patients than controls (P < 0.0001). There were significant differences of serum MCP-1 level between patients of the GG genotype and the AA genotype (P = 0.028), between patients of the AG genotype and the AA genotype (P = 0.049), and between patients of the AG + GG genotype and the AA genotype (P = 0.027). These results showed the -2518 MCP-1 polymorphism is related to the susceptibility of plaque type psoriasis. Individuals containing the GG or AG genotype were at higher risk of psoriasis than subjects with the AA genotype.     

Association of MCP-1 promotor polymorphism with disease severity of Crimean-Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF) is a thick-borne viral zoonotic disease. The pathogenesis and the reasons why cases have a mild or severe course in CCHF have not yet been explained. In this study, we investigated the relationship between promoter -2518 A/G single-nucleotide polymorphism (SNP) of the MCP-1 gene and the clinical course of CCHF. The MCP-1-2518 A/G SNP (rs1024611) frequency was examined in 128 virologically/serologically confirmed CCHF patients and 181 healthy controls by using the PCR-RFLP method. When CCHF patients and controls were compared, no significant difference was found between genotype distributions and allele frequencies of the -2518 A/G SNP of MCP-1 gene (P > .05). Compared to the AA genotype, both AG (P = .016; OR = 2.57) and GG genotype (P = .039; OR = 3.43) were found with significantly higher frequencies in mild/moderate cases than in severe cases. Compared to the AG + GG genotype, AA showed a significant risk for severe CCHF (60.0% vs 38.4%, P = .02; OR = 2.41). In contrast, the AG genotype showed a significant protective effect against severe disease compared to AA + GG genotype (29.1% vs 47.9%, P = .013; OR = 2.58). Compared to mild/moderate cases, the A allele was found to be significantly higher in severe cases (0.745 vs 0.623, P = .039; OR = 1.77). However, no significant relationship was found between fatal and nonfatal cases in terms of genotype or allele frequencies (P > .05). In conclusion, both -2518 AA genotype and A allele of MCP-1 were associated with disease severity, and the AG genotype had a protective effect against a severe disease course in CCHF patients.     

MCP-1 promoter polymorphism in Spanish patients with systemic lupus erythematosus

The possible role of the functional polymorphism located in the regulatory region of the monocyte chemoattractant protein-1 (MCP-1) gene in the susceptibility to systemic lupus erythematosus (SLE) was investigated. Two hundred and seventy-six SLE patients (among them, 99 with lupus nephritis and 55 with cutaneous vasculitis) and 194 ethnically matched healthy controls were included in the study. Genotyping for -2518 (A/G) MCP-1 gene polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No association between -2518 (A/G) MCP-1 polymorphism and susceptibility to SLE nor to lupus nephritis was found. However, a significant increase in the frequency of genotype AG and a decrease in the frequency of genotype AA were found among patients with cutaneous vasculitis (51% of AG vs. 32% in individuals without cutaneous vasculitis; P=0.008, OR=2.2, 95% CI: 1.18-4.25; and 47% of AA vs. 64%; P=0.03, OR=0.5, 95% CI: 0.27-0.96, respectively). These results indicate an association between the presence of G at position -2518 in the MCP-1 promoter region and the presence of cutaneous vasculitis among patients with SLE. This polymorphism does not seem to influence the susceptibility to SLE nor the appearance of lupus nephritis. Further studies are necessary in order to elucidate the role of this polymorphism in the pathogenesis of other inflammatory autoimmune diseases.     

Association of MCP-1 and CCR2 polymorphisms with the risk of late acute rejection after renal transplantation in Korean patients

Among the factors modulating transplant rejection, chemokines and their respective receptors deserve special attention. Increased expression of monocyte chemoattractant protein-1 (MCP-1) and its corresponding receptor (chemokine receptor-2, CCR2) has been implicated in renal transplant rejection. To determine the impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function, 167 Korean patients who underwent transplantation over a 25-year period were evaluated. Genomic DNA was genotyped using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Fifty-five (32.9%) patients were homozygous for the MCP-1-2518G polymorphism. Nine (5.4%) patients were homozygous for the CCR2-64I polymorphism. None of the investigated polymorphism showed a significant shift in long-term allograft survival. However, a significant increase was noted for the risk of late acute rejection in recipients who were homozygous for the MCP-1-2518G polymorphism (OR, 2.600; 95% CI, 1.125-6.012; P = 0.022). There was also an association between the MCP-1-2518G/G genotype and the number of late acute rejection episodes (P = 0.024). Although there was no difference in the incidence of rejection among recipients stratified by the CCR2-V64I genotype, recipients with the CCR2-V64I GG genotype in combination with the MCP-1-2518G/G genotype had a significantly higher risk of acute or late acute rejection among the receptor-ligand combinations (P = 0.006, P = 0.008, respectively). The MCP-1 variant may be a marker for risk of late acute rejection in Korean patients.     

The TNF-alpha -308, MCP-1 -2518 and TGF-beta1 +915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants

Chronic lung disease (CLD) in premature newborns is associated with increased concentrations of inflammatory cytokines in tracheal aspirates (TA). We determined if polymorphisms of cytokine genes influence the risk of developing CLD by genotyping 178 mechanically ventilated very low birth weight (VLBW) infants for the tumor necrosis factor-alpha (TNF-alpha) -308 G/A, transforming growth factor-beta(1) (TGF-beta(1)) +915 G/C and monocyte chemoattractant protein-1 (MCP-1) -2518 A/G polymorphisms. Genomic DNA was isolated from TA and genotypes determined by restriction length polymorphism. There was no effect of any of these polymorphisms on the development of CLD (29 vs 23%, P=0.371, TNF-alpha -308 AA/AG vs TNF-alpha -308 GG; 23 vs 26%, P=0.681, MCP-1 -2518 GG/AG vs MCP-1 -215-8 AA; 24 vs 24%, P=0.978, TGF-beta(1) +915 CG vs TGF-beta(1) +915 GG). TA IL-8 and MCP-1 concentrations were not different between genotype groups. Infants with the TNF-alpha -308 A allele had increased risk of IVH (RR 2.07; 95% CI 1.02-4.18, P=0.041) and infants with the TGF-beta(1) +915 C allele were at greater risk of death (32 vs 9%, P=0.016). These data suggest that these polymorphisms do not play a significant role in determining risk for CLD in preterm infants, but may play a role in other complications in the neonatal period.     

MCP-1 promoter polymorphism in Spanish patients with rheumatoid arthritis

To investigate the possible role of the polymorphism located in the regulatory region of monocyte chemoattractant protein-1 (MCP-1) gene in the susceptibility to rheumatoid arthritis (RA), a total of 141 Spanish RA patients and 194 controls, previously typed for human leukocyte antigen DRB1* (HLA-DRB1*), were genotyped for -2518 (A/G) MCP-1 gene polymorphism using polymerase chain reaction-restriction fragment length polymorphism. No association between -2518 (A/G) MCP-1 polymorphism and susceptibility to RA was found. Nevertheless, when patients and controls were stratified according to their HLA shared epitope (SE) status, a significant increase in the frequency of genotype GG was found among SE negative (SE-) patients with respect to both SE positive (SE+) patients and SE- controls (16% versus 4% in SE+ patients, pFisher=0.04, odds ratio [OR]=4.4, 95% confidence interval [95%CI]=1.03-21.48; and 4% in SE- controls, pFisher=0.02, OR=4.13, 95%CI=1.10-15.72). In conclusion, MCP-1 polymorphism is slightly associated with the susceptibility to RA in patients lacking the HLA SE.     

Lack of association between DNA repair gene ERCC1 polymorphism and risk of lung cancer in a Chinese population

The ERCC1 (Excision Repair Cross Complementation Group 1) gene is involved in the nucleotide excision repair pathway. This study was designed to examine whether ERCC1 Asn118Asn (G19007A) polymorphism, which has been associated with risk of some cancers among Caucasians, may be associated with risk of lung cancer in a Chinese population. ERCC1 Asn118Asn (G19007A) genotypes were determined in DNA samples from 151 cases and 143 controls. The distribution of genotypes between cases and controls was not associated with an increased risk of lung cancer (AA versus GG: adjusted OR (odds ratio) = 1.41, 95% CI (confidence interval) = 0.76-2.59; AG versus GG: adjusted OR = 0.78, 95% CI = 0.47-1.29; and AA + AG versus GG: adjusted OR = 0.93, 95% CI = 0.73-1.19). The frequency A (0.20) of the A-allele was significantly lower among these Chinese controls than in the Caucasian control populations (A = 0.54-0.65) (All P < 0.001). No statistically significant effects of age, histological subtype or smoking were found. These findings suggest that ERCC1 Asn118Asn (G19007A) polymorphism may play a limited role for lung cancer in this Chinese population.     

Association of the A/G polymorphism at position 49 in exon 1 of CTLA-4 with the susceptibility to unexplained recurrent spontaneous abortion in the Chinese population

PROBLEM: To investigate whether the A/G polymorphism at position 49 in exon 1 of cytotoxic T lymphocyte antigen-4 (CTLA-4) gene, which delivers a negative signal to T-cell activation, confers the susceptibility to unexplained recurrent spontaneous abortion in the Chinese population. METHOD OF STUDY: A total of 168 patients with unexplained recurrent spontaneous abortion (RSA), who were treated in the Renji Hospital affiliated to the Shanghai Second Medical University, were matched against 117 women with normal pregnancy history. Case-control study to compare the frequency of G/A alleles, AA/AG/GG genotypes and A + (AA + AG) /G+ (GG + AG) phenotypes of CTLA-4 between RSA patients and controls were performed. After amplification of CTLA-4 exon-1 region by polymerase chain reaction (PCR), restriction fragment-length polymorphism (RFLP) was used to detect the polymorphism at position 49 in exon-1 of CTLA-4 gene. Statistical significance was tested by SPSS software. RESULTS: There were dissimilar distributions of G/A alleles, AA/AG/GG genotypes and A+/G+ phenotypes of CTLA-4 between RSA patients and controls. The frequencies of G allele (P = 0.032) and GG genotype (P = 0.011) in RSA patients were significantly higher than those in controls, while the frequencies of AG genotype (P = 0.039) and A + (AA + AG) phenotype in RSA patients were decreased significantly (P = 0.011). CONCLUSIONS: Our findings suggest that A/G polymorphism in exon-1 of CTLA-4 is associated with the immunopathogenesis of RSA, and it confers susceptibility to RSA in Chinese population.     

2型糖尿病家系与尾加压素2基因多态性

目的探讨我国常州地区汉族家系2型糖尿病与尾加压素2(urotensinⅡ,UT-Ⅱ)基因rs228648多态性位点的关系。方法采用家系内外对照的病例对照研究,并设置无家族史的普通病例组,应用聚合酶链反应-限制性片段长度多态性技术,对rs228648(G/A)多态性进行基因分型。结果家系中携带AG和AA基因型者患病风险分别为GG型的1.98(95%可信区间=1.19～3.29)和2.46(95%可信区间=1.39～4.34)倍,家系病例组A等位基因频率高于内对照组及普通病例组(P=0.01)。内对照组A等位基因频率高于外对照组(P=0.001)。内对照组携带AG基因型者的胰岛素抵抗指数、胰岛素敏感指数以及胰岛初期分泌功能指数均高于GG基因型者(P<0.05)。结论rs228648多态性位点变异可能是2型糖尿病的危险因素之一,家系人群该基因变异与其胰岛功能间存在关联。