| Part I Calcium-Sensing Receptor Genetic Polymorphisms and Risk of Developing NephrolithiasisObjective To evaluate the association between CASR Arg990Gly(rs 1042636,A>G),Ala986Ser(rs1801725,G>T)polymorphisms and nephrolithiasis risk.Materials and methods The hospital-based case-control study was consisted of 615 nephrolithiasis cases and 315 controls.All the subjects were unrelated Han Chinese.Briefly,all cases were confirmed to have nephrolithiasis by X-ray,type-B ultrasonic and CT detection at the time of enrollment in our ongoing study,and were recruited from the Changshu Hospital Affiliated to Soochow University and Huaiyin Hospital(Huai-An)starting from March 2010 to January 2015.Genomic DNA was isolated from peripheral blood cells by a QIAamp DNA Blood Maxi kit.The CASR Arg990Gly and Ala986Ser polymorphisms were genotyped using SNaPshot method.Stone composition was assessed through Fourier-transformed infrared spectrophotometry.Fasting blood samples were taken from the cases and controls to measure their plasma biochemistry indexes such as serum calcium,serum creatinine and serum uric acid on automatic clinical chemistry analyzer.Statistical analysis system software was used for all statistical analyses,and a two-sided P<0.05 was considered to reach statistical significance.The Pearson’s χ2 test and Student’s t-test were applied to check the differences in the selected variables and distributions of demographic characteristics between cases and controls.The association between the nephrolithiasis risk and genotypes was estimated by using adjusted odds ratios(ORs)and 95%confidence intervals(CIs)from unconditional logistic regression.All ORs were adjusted for age,sex,cigarette smoking,and drinking status.Results The cases and controls appeared to be well matched on age:mean age was 48.0±12.0 years for the cases and 47.6±11.4 years for the controls(P=0.606).The sex distributions were similar(P=0.182)among cases and controls.More smokers were found among the cases than among the controls(P=0.026),suggesting that smoking may play a role in the etiology of nephrolithiasis.In addition,compared with controls,more patients were diagnosed as hypertension in cases(P<0.001).For Arg990Gly polymorphism,the frequencies of the AA,AG,and GG genotypes were 17.7%,56.6%,25.7%,respectively,among the cases;and they were 24.1%,54.6%,21.3%,respectively,among the controls(P=0.047).When we used the Arg990Gly AA genotype as the reference,we found that individuals with GG genotype were associated with a statistically significantly increased risk of nephrolithiasis(adjusted OR=1.64,95%CI=1.08-2.50).Compared with the AA genotype,the combined variant genotypes AG/GG was found to be associated with a significantly increased risk of nephrolithiasis(adjusted OR=1.45,95%Cl=1.04-2.03).The stratified analyses showed that the risk remained for subgroup of age>48,never smokers,patients with hypertension and calcium oxalate stones(OR 1.78,95%CI:1.02-3.09;OR 1.54,95%CI:1.03-2.30;OR 2.83,95%CI:1.32-6.07;OR 1.60,95%CI:1.12-2.28,respectively).However,the frequencies of Ala986Ser genotypes have no statistical differences between the cases and controls(P=1.000).In addition,we conducted an analysis to access the association between the Arg990Gly polymorphism and plasma biochemistry indexes such as serum calcium,serum creatinine and serum uric acid.No significant association was found between Arg990Gly polymorphism and plasma biochemistry indexes.In stratification analyses,no significant association was found between Arg990Gly polymorphism and hypercalcemia,hyperuricemia and high level of blood creatinine.Conclusion Our results provide evidences that the CASR Arg990Gly polymorphism is associated with nephrolithiasis risk and thus may be used as a risk marker in nephrolithiasis.Part Ⅱ Association between Dyslipidemia and Nephrolithiasis RiskObjective To evaluate the association between dyslipidemia and nephrolithiasis.Materials and Methods The hospital-based case-control study was consisted of 540 nephrolithiasis cases and 656 kidney stone-free controls.All the subjects were unrelated Han Chinese.All cases were confirmed to have nephrolithiasis by X-ray,type-B ultrasonic and CT detection at the time of enrollment in our ongoing study,and were recruited from the Changshu Hospital Affiliated to Soochow University between Jan 2012 and Apr 2018.Patients who had tumor,thyroid or parathyroid disease,a history of taking lipid-lowering drugs were excluded from this research.Fasting venous blood were drawn from the cases and controls for determining their plasma lipid profiles.Total cholesterol(TC),triglycerides(TG),and high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)were tested by enzymatic methods on automatic clinical chemistry analyzer.The stones extracted from the patients were gathered following the operation.Stone composition was assessed through Fourier-transformed infrared spectrophotometry.Statistical analysis system software was used for all statistical analyses,and a two-sided P<0.05 was considered to reach statistical significance.The Pearson’s χ2 test or Fisher’s exact test and Student’s t-test were applied to check the differences in the selected variables and distributions of demographic characteristics between cases and controls.The association between the nephrolithiasis risk and dyslipidemia was estimated by using adjusted odds ratios(ORs)and 95%confidence intervals(CIs)from unconditional logistic regression analysis.All ORs were adjusted for age,sex,BMI,and hypertension and diabetes mellitus status.Results The cases and controls appeared to be well matched on age:mean age was(55.70±14.00)years for the cases and(54.32±17.77)years for the controls(P=0.134).The cases and controls appeared to be well matched on age and sex distribution.However,the BMI of the cases(24.30 ±2.08)were significantly higher than the control group(23.77±2.34)(P<0.001).More hypertension were found among the cases than the controls(34.07%and 23.93%,respectively),the difference with statistically significance(P<0.001).Compared with the control group,the cases with nephrolithiasis were found to have significantly higher TG levels(132.83 ± 97.67 mg/dL for cases,115.47±55.82 mg/dL for controls,P<0.001)but lower TC(175.81±36.26 mg/dL for cases,182.72±34.01 mg/dL for controls,P<0.001),HDL-C(43.68±13.82 mg/dL for cases,54.16±11.76 mg/dL for controls,P<0.001)and LDL-C levels(94.48±26.75 mg/dL for cases,102.91±24.80 mg/dL for controls,P<0.001).Significantly higher TG levels but lower HDL-C,LDL-C levels were found in both primary and recurrent nephrolithiasis patients compared with controls.Compared to the controls,primary rather than recurrent nephrolithiasis patients had significantly lower TC levels.In subgroup analysis by stone composition,significantly lower TC and LDL-C levels were found in all patients except those with uric acid stones.Significantly higher TG levels were found in patients with CaOx and uric acid stones.Patients with any kind of stone composition were found to have significantly lower HDL-C levels.When we analyzed the association between dyslipidemia status and nephrolithiasis,we found that individuals with hypertriglyceridemia and low HDL-cholesterolemia were associated with increased risks of nephrolithiasis(adjusted OR=1.31,95%CI=1.01-1.71 and adjusted OR=7.57,95%CI=5.64-10.17,respectively).In contrast,individuals with hypercholesterolemia and high LDL-cholesterolemia were associated with decreased risks of nephrolithiasis(adjusted OR=0.60,95%CI=0.46-0.79 and adjusted OR=0.61,95%CI=0.42-0.90,respectively).In the stratified analysis by chemical stone composition,hypercholesterolemia was found to be associated with decreased risk in patients with CaOx and infection stones.Hypertriglyceridemia is associated with higher risk of CaOx stones while high LDL-cholesterolemia is associated with lower risk of CaOx stones.Low HDL-cholesterolemiamia was found to be associated with increased risk in patients with any kind of stone composition.Conclusions Our findings indicated that dyslipidemia including hypertriglyceridemia,low HDL-cholesterolemia,hypercholesterolemia and high LDL-cholesterolemia was associated with nephrolithiasis risk,especially in patients with CaOx.Larger prospective studies are needed to confirm the results. |
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