Li Yongyuan, Ding Yuanlin, Jing Shusen, Su Feng, Shao Jianping
Department of General Surgery, Tianjin Fifth Central Hospital, Tianjin 300450, China. Corresponding author: Shao Jianping, Email:
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Oct;35(10):1058-1062. doi: 10.3760/cma.j.cn121430-20230307-00145.
To investigate the effect of vitamin D binding protein (DBP) gene polymorphism on susceptibility and prognosis of severe acute pancreatitis (SAP).
A prospective study was conducted. Eighty-three patients with SAP who were admitted to the department of general surgery of Tianjin Fifth Central Hospital from March 2018 to March 2021 were selected as the research objects, and 83 healthy people in the same period were selected as controls. Peripheral blood RNA was extracted and reverse transcribed into cDNA, and the genotype and allele frequency of DBP gene rs7041 locus were detected by fluorescence quantitative analyzer. Hardy-Weinberg equilibrium was used to test the genetic balance. On the day of admission, serum C-reactive protein (CRP) level was detected by scattering immunoturbidimetry, serum procalcitonin (PCT) level was detected by electrochemiluminescence, serum DBP level was detected by enzyme-linked immunosorbent assay (ELISA), and neutrophil to lymphocyte ratio (NLR) was calculated automatically by the instrument. The length of intensive care unit (ICU) stay, the length of hospital stay and prognosis during hospitalization of patients were statistically analyzed. Multivariate Logistic regression analysis was used to screen the influencing factors of SAP occurrence.
The results of Hardy-Weinberg equilibrium test showed that the distribution of gene polymorphisms in the two groups of subjects conformed to the law of genetic equilibrium. The frequencies of TT genotype and T allele of DBP gene rs7041 locus in the patients of SAP group were significantly higher than those in the healthy control group [TT genotype: 34.94% (29/83) vs. 9.64% (8/83), T allele: 55.42% (92/166) vs. 38.55% (64/166), both P < 0.01], and the frequency of GT genotype was significantly lower than that in the healthy control group [40.96% (34/83) vs. 57.83% (48/83), P < 0.05]. There was no significant difference in the frequency of GG genotype between the healthy control group and SAP group [32.53% (27/83) vs. 24.10% (20/83), P > 0.05]. Further multivariate Logistic regression analysis showed that TT genotype [odds ratio (OR) = 2.831, 95% confidence interval (95%CI) was 1.582-5.067, P < 0.001] and T allele (OR = 2.533, 95%CI was 1.435-4.472, P < 0.001) of DBP gene rs7041 locus were independent risk factors for SAP in healthy people, while GT genotype was a protective factor for SAP (OR = 0.353, 95%CI was 0.143-0.868, P = 0.041). The levels of CRP, PCT, NLR and DBP in patients with TT genotype of DBP gene rs7041 locus were significantly higher than those in patients with GG/GT genotype on the day of admission in SAP group [CRP (mg/L): 43.25±13.25 vs. 31.86±12.83, PCT (μg/L): 1.53±0.24 vs. 1.21±0.20, NLR: 3.15±0.53 vs. 2.71±0.48, DBP (μg/L): 87.78±19.64 vs. 70.58±18.67, all P < 0.01]. The length of ICU stay in patients with TT genotype of DBP gene rs7041 locus in SAP group was significantly longer than that in patients with GG/GT genotype (days: 11.35±1.58 vs. 9.71±1.35, P < 0.01). The length of hospital stay of patients with TT genotype was longer than that of patients with GG/GT genotype (days: 23.41±3.64 vs. 23.17±3.57), and the in-hospital mortality was higher than that of patients with GG/GT genotype [34.48% (10/29) vs. 29.63% (16/54)], but the difference was not statistically significant (both P > 0.05).
The risk of SAP was significantly increased in patients with TT genotype of rs7041 locus of DBP gene, and the mechanism may be related to the increase of DBP expression. And carrying the TT genotype will prolong the ICU hospitalization time of SAP patients, but the effect on prognosis is not obvious.
探讨维生素D结合蛋白(DBP)基因多态性对重症急性胰腺炎(SAP)易感性及预后的影响。
进行一项前瞻性研究。选取2018年3月至2021年3月在天津市第五中心医院普通外科住院的83例SAP患者作为研究对象,同期选取83例健康人作为对照。提取外周血RNA并逆转录为cDNA,采用荧光定量分析仪检测DBP基因rs7041位点的基因型及等位基因频率。采用Hardy-Weinberg平衡检验基因平衡情况。入院当天,采用散射免疫比浊法检测血清C反应蛋白(CRP)水平,采用电化学发光法检测血清降钙素原(PCT)水平,采用酶联免疫吸附试验(ELISA)检测血清DBP水平,仪器自动计算中性粒细胞与淋巴细胞比值(NLR)。对患者的重症监护病房(ICU)住院时间、住院时间及住院期间的预后进行统计学分析。采用多因素Logistic回归分析筛选SAP发生的影响因素。
Hardy-Weinberg平衡检验结果显示,两组研究对象的基因多态性分布符合遗传平衡定律。SAP组患者DBP基因rs7041位点的TT基因型和T等位基因频率显著高于健康对照组[TT基因型:34.94%(29/83) vs. 9.64%(8/83),T等位基因:55.42%(92/166) vs. 38.55%(64/166),均P<0.01],GT基因型频率显著低于健康对照组[40.96%(34/83) vs. 57.83%(48/83),P<0.05]。健康对照组与SAP组GG基因型频率比较,差异无统计学意义[32.53%(27/83) vs. 24.10%(20/83),P>0.05]。进一步多因素Logistic回归分析显示,DBP基因rs7041位点的TT基因型[比值比(OR)=2.831,95%置信区间(95%CI)为1.582 - 5.067,P<0.001]和T等位基因(OR = 2.533,95%CI为1.435 - 4.472,P<0.001)是健康人群发生SAP的独立危险因素,而GT基因型是SAP的保护因素(OR = 0.353,95%CI为0.143 - 0.868,P = 0.041)。SAP组中DBP基因rs7041位点TT基因型患者入院当天的CRP、PCT、NLR及DBP水平显著高于GG/GT基因型患者[CRP(mg/L):43.25±13.25 vs. 31.86±12.83,PCT(μg/L):1.53±0.24 vs. 1.21±0.20,NLR:3.15±0.53 vs. 2.71±0.48,DBP(μg/L):87.78±19.64 vs. 70.58±18.67,均P<0.01]。SAP组中DBP基因rs7041位点TT基因型患者的ICU住院时间显著长于GG/GT基因型患者(天:11.35±1.58 vs. 9.71±1.35,P<0.01)。TT基因型患者的住院时间长于GG/GT基因型患者(天:23.41±3.64 vs. 23.17±3.57),院内死亡率高于GG/GT基因型患者[34.48%(10/29) vs. 29.63%(16/54)],但差异无统计学意义(均P>0.05)。
DBP基因rs7041位点TT基因型患者发生SAP的风险显著增加,机制可能与DBP表达增加有关。携带TT基因型会延长SAP患者的ICU住院时间,但对预后的影响不明显。